Skip to main content
SpringerLink
Log in
Book cover

Lung Inflammation in Health and Disease, Volume II pp 147–164Cite as

Overview on Interactive Role of Inflammation, Reactive Oxygen Species, and Calcium Signaling in Asthma, COPD, and Pulmonary Hypertension

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1304))

Abstract

Inflammatory signaling is a major component in the development and progression of many lung diseases, including asthma, chronic obstructive pulmonary disorder (COPD), and pulmonary hypertension (PH). This chapter will provide a brief overview of asthma, COPD, and PH and how inflammation plays a vital role in these diseases. Specifically, we will discuss the role of reactive oxygen species (ROS) and Ca2+ signaling in inflammatory cellular responses and how these interactive signaling pathways mediate the development of asthma, COPD, and PH. We will also deliberate the key cellular responses of pulmonary arterial (PA) smooth muscle cells (SMCs) and airway SMCs (ASMCs) in these devastating lung diseases. The analysis of the importance of inflammation will shed light on the key questions remaining in this field and highlight molecular targets that are worth exploring. The crucial findings will not only demonstrate the novel roles of essential signaling molecules such as Rieske iron-sulfur protein and ryanodine receptor in the development and progress of asthma, COPD, and PH but also offer advanced insight for creating more effective and new therapeutic targets for these devastating inflammatory lung diseases.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

ASK1:

Apoptosis signal-regulating kinase 1

ASMC:

Airway smooth muscle cell

ATM:

Ataxia-telangiectasia mutated

BALF:

Bronchoalveolar lavage fluid

CaM:

Calmodulin

CDK:

Cyclin-dependent kinase

CICR:

Calcium-induced calcium release

CIRG:

Calcium-induced ROS generation

COPD:

Chronic obstructive pulmonary disease

CS:

Cigarette smoke

DAG:

Diacylglycerol

DAMP:

Damage-associated molecular pattern

ECM:

Extracellular matrix

ETC:

Electron transport chain

GPCR:

G protein-coupled receptor

Gpx:

Glutathione peroxidase

GSH:

Glutathione

HIF-1α:

Hypoxia-inducible factor-1α

HPV:

Hypoxic pulmonary vasoconstriction

IKK:

IκB kinase

IP3:

Inositol triphosphate

IP3R:

Inositol-1,4,5-triphosphate receptor

Kv:

Voltage-gated potassium

LTCC:

L-type voltage-gated calcium channel

MAPK:

Mitogen-activated protein kinase

MLCK:

Myosin light chain kinase

MMP:

Matrix metalloproteinases

nAChR:

Nicotinic acetylcholine receptor

NADPH:

Nicotinamide dinucleotide phosphate

NEMO:

NF-κB essential modulator

NF-κB:

Nuclear factor-κB

NIK:

NF-κB-inducing kinase

NLR:

NOD-like receptor

NOS:

Nitric oxide synthase

PA:

Pulmonary artery

PAMP:

Pathogen-associated molecular pattern

PH:

Pulmonary hypertension

PKC:

Protein kinase C

PPA:

Pulmonary arterial pressure

PRR:

Pattern recognition receptor

PVR:

Pulmonary vascular resistance

RHD:

Rel homology domain

RICR:

ROS-induced calcium release

RISP:

Rieske iron-sulfur protein

ROS:

Reactive oxygen species

RyR:

Ryanodine receptor

SMC:

Smooth muscle cells

SR:

Sarcoplasmic reticulum

TAK1:

TGF-β-activated kinase 1

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

TRP:

Transient receptor potential

TRPC:

Canonical TRP

References

  1. Chaouat A, Naeije R, Weitzenblum E. Pulmonary hypertension in COPD. Eur Respir J. 2008;32(5):1371–85.

    Article  CAS  PubMed  Google Scholar 

  2. Devine JF. Chronic obstructive pulmonary disease: an overview. Am Health Drug Benefits. 2008;1(7):34–42.

    PubMed  PubMed Central  Google Scholar 

  3. Quirt J, et al. Asthma. Allergy Asthma Clin Immunol. 2018;14(Suppl 2):50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Prevention, C.f.D.C.a. Chronic Obstructive Pulmonary Disease (COPD). 2018.

    Google Scholar 

  5. Bush A. Pathophysiological mechanisms of asthma. Front Pediatr. 2019;7:68.

    Article  PubMed  PubMed Central  Google Scholar 

  6. NIH. COPD 2019.

    Google Scholar 

  7. Peter J, Barnes PGB, Silverman EK, Celli BR, Vestbo J, Wedzicha JA, Wouters EFM. Chronic obstructive pulmonary disease. Nature. 2015;1(15076)

    Google Scholar 

  8. Disease, G.I.f.C.O.L., Pocket guide to COPD diagnosis, management, and prevention, Hadfield R, editor. 2017.

    Google Scholar 

  9. Natalie Terzikhan KMCV, Hofman A, Stricker BH, Brusselle GG, Lahousse L. Prevalence and incidence of COPD in smokers and non-smokers: the Rotterdam study. Eur J Epidemiol. 2016;31(8):785–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Elwing J, Panos RJ. Pulmonary hypertension associated with COPD. Int J Chron Obstruct Pulmon Dis. 2008;3(1):55–70.

    PubMed  PubMed Central  Google Scholar 

  11. Sara Roversi LMF, Sin DD, Hawkins NM, Agusti A. Chronic obstructive pulmonary disease and cardiac diseases. Am J Respir Crit Care Med. 2016;194(11):1319–36.

    Article  PubMed  Google Scholar 

  12. Nathaniel M, Hawkins MCP, Jhund PS, Chalmers GW, Dunn FG, McMurray JJV. Heart failure and chronic obstructive pulmonary disease: diagnostic pitfalls and epidemiology. Eur J Heart Fail. 2009;11(2):130–9.

    Article  Google Scholar 

  13. Jeremy A, Falk SK, Criner GJ, Scharf SM, Minaj OA, Diaz P. Cardiac disease in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5(4):543–8.

    Article  Google Scholar 

  14. Barberà JA, Peinado VI, Santos S. Pulmonary hypertension in chronic obstructive pulmonary disease. Eur Respir J. 2003;21(5):892.

    Article  PubMed  Google Scholar 

  15. Subbarao P, Mandhane PJ, Sears MR. Asthma: epidemiology, etiology and risk factors. CMAJ. 2009;181(9):E181–90.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Julio D, Antuni APJB. Evaluation of individuals at risk for COPD: beyond the scope of the global initiative for chronic obstructive lung disease. Chronic Obstr Pulm Dis. 2016;3(3):653–67.

    Google Scholar 

  17. Laniado-Laborin R. Smoking and chronic obstructive pulmonary disease (COPD). Parallel epidemics of the 21st century. Int J Environ Res Public Health. 2009;6(1):209–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Marsh S, Aldington S, Shirtcliffe P, Weatherall M, Beasley R. Smoking and COPD: what really are the risks? Eur Respir J. 2006;28:883–6.

    Article  CAS  PubMed  Google Scholar 

  19. Page C, Cazzola M. Bifunctional drugs for the treatment of asthma and chronic obstructive pulmonary disease. Eur Respir J. 2014;44(2):475.

    Article  CAS  PubMed  Google Scholar 

  20. Ernst P, Saad N, Suissa S. Inhaled corticosteroids in COPD: the clinical evidence. Eur Respir J. 2015;45:525–37.

    Article  CAS  PubMed  Google Scholar 

  21. Keglowich LF, Borger P. The three A’s in asthma – airway smooth muscle, airway remodeling & angiogenesis. Open Respir Med J. 2015;9:70–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. James AL, Wenzel S. Clinical relevance of airway remodelling in airway diseases. Eur Respir J. 2007;30(1):134.

    Article  CAS  PubMed  Google Scholar 

  23. Khan MA. Inflammation signals airway smooth muscle cell proliferation in asthma pathogenesis. Multidiscip Respir Med. 2013;8(1):11.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Salter B, et al. Regulation of human airway smooth muscle cell migration and relevance to asthma. Respir Res. 2017;18(1):156.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Goncharova EA, et al. Cyclic AMP-mobilizing agents and glucocorticoids modulate human smooth muscle cell migration. Am J Respir Cell Mol Biol. 2003;29(1):19–27.

    Article  CAS  PubMed  Google Scholar 

  26. Crosswhite P, Sun Z. Molecular mechanisms of pulmonary arterial remodeling. Mol Med (Cambridge, Mass). 2014;20(1):191–201.

    Article  CAS  Google Scholar 

  27. Churg A, Zhou S, Wright JL. Matrix metalloproteinases in COPD. Eur Respir J. 2012;39(1):197.

    Article  CAS  PubMed  Google Scholar 

  28. Vandenbroucke RE, Dejonckheere E, Libert C. A therapeutic role for matrix metalloproteinase inhibitors in lung diseases? Eur Respir J. 2011;38(5):1200.

    Article  CAS  PubMed  Google Scholar 

  29. Zhu J, et al. Reactive oxygen species-dependent Calpain activation contributes to airway and pulmonary vascular remodeling in chronic obstructive pulmonary disease. Antioxid Redox Signal. 2019;

    Google Scholar 

  30. Churg A, et al. Cigarette smoke drives small airway remodeling by induction of growth factors in the Airway Wall. Am J Respir Crit Care Med. 2006;174(12):1327–34.

    Article  CAS  PubMed  Google Scholar 

  31. Boukhenouna S, et al. Reactive oxygen species in chronic obstructive pulmonary disease. Oxidative Med Cell Longev. 2018;2018:5730395.

    Article  CAS  Google Scholar 

  32. Circu ML, Aw TY. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 2010;48(6):749–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Smith KA, Waypa GB, Schumacker PT. Redox signaling during hypoxia in mammalian cells. Redox Biol. 2017;13:228–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417(1):1–13.

    Article  CAS  PubMed  Google Scholar 

  35. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014;94(3):909–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Dröse S, Brandt U. Molecular mechanisms of superoxide production by the mitochondrial respiratory chain. In: Kadenbach B, editor. Mitochondrial oxidative phosphorylation: nuclear-encoded genes, enzyme regulation, and pathophysiology. New York: Springer New York; 2012. p. 145–69.

    Chapter  Google Scholar 

  37. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552(Pt 2):335–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Diaz F, Enríquez JA, Moraes CT. Cells lacking Rieske iron-sulfur protein have a reactive oxygen species-associated decrease in respiratory complexes I and IV. Mol Cell Biol. 2012;32(2):415–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Korde AS, et al. Primary role of mitochondrial Rieske iron-sulfur protein in hypoxic ROS production in pulmonary artery myocytes. Free Radic Biol Med. 2011;50(8):945–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Truong L, Zheng Y-M, Wang Y-X. Mitochondrial Rieske iron-sulfur protein in pulmonary artery smooth muscle: a key primary signaling molecule in pulmonary hypertension. Arch Biochem Biophys. 2019;664:68–75.

    Article  CAS  PubMed  Google Scholar 

  41. Wang Y-X, et al. Rieske iron-sulfur protein in mitochondrial complex III is essential for the heterogeneity of hypoxic cellular responses in pulmonary and systemic (mesenteric) artery smooth muscle cells. FASEB J. 2015;29(1_supplement):859.1.

    Google Scholar 

  42. Görlach A, et al. Calcium and ROS: a mutual interplay. Redox Biol. 2015;6:260–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Meitzler JL, et al. NADPH oxidases: a perspective on reactive oxygen species production in tumor biology. Antioxid Redox Signal. 2014;20(17):2873–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Rastogi R, et al. NOX activation by subunit interaction and underlying mechanisms in disease. Front Cell Neurosci. 2017;10:301.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Cosentino-Gomes D, Rocco-Machado N, Meyer-Fernandes JR. Cell signaling through protein kinase C oxidation and activation. Int J Mol Sci. 2012;13(9):10697–721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Di Meo S, et al. Role of ROS and RNS sources in physiological and pathological conditions. Oxidative Med Cell Longev. 2016;2016:–1245049.

    Google Scholar 

  47. Feno S, et al. Crosstalk between calcium and ROS in pathophysiological conditions. Oxidative Med Cell Longev. 2019;2019:9324018.

    Article  CAS  Google Scholar 

  48. Hempel N, Trebak M. Crosstalk between calcium and reactive oxygen species signaling in cancer. Cell Calcium. 2017;63:70–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhang J, et al. ROS and ROS-mediated cellular signaling. Oxidative Med Cell Longev. 2016;2016:4350965.

    Article  Google Scholar 

  50. Gordeeva AV, Zvyagilskaya RA, Labas YA. Cross-talk between reactive oxygen species and calcium in living cells. Biochem Mosc. 2003;68(10):1077–80.

    Article  CAS  Google Scholar 

  51. Mondola P, et al. The cu, Zn superoxide dismutase: not only a dismutase enzyme. Front Physiol. 2016;7:594.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Morgan MJ, Liu Z-G. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res. 2011;21(1):103–15.

    Article  CAS  PubMed  Google Scholar 

  53. Banan A, et al. Phospholipase C-γ inhibition prevents EGF protection of intestinal cytoskeleton and barrier against oxidants. Am J Physiol Gastrointest Liver Physiol. 2001;281(2):G412–23.

    Article  CAS  PubMed  Google Scholar 

  54. Wang Y-X, Zheng Y-M. Role of ROS signaling in differential hypoxic Ca2+ and contractile responses in pulmonary and systemic vascular smooth muscle cells. Respir Physiol Neurobiol. 2010;174(3):192–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Valavanidis A, Vlachogianni T, Fiotakis K. Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles. Int J Environ Res Public Health. 2009;6(2):445–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. McGuinness AJA, Sapey E. Oxidative stress in COPD: sources, markers, and potential mechanisms. J Clin Med. 2017;6(2):21.

    Article  PubMed Central  CAS  Google Scholar 

  57. Rahman I, Adcock IM. Oxidative stress and redox regulation of lung inflammation in COPD. Eur Respir J. 2006;28(1):219.

    Article  CAS  PubMed  Google Scholar 

  58. Liu X, Chen Z. The pathophysiological role of mitochondrial oxidative stress in lung diseases. J Transl Med. 2017;15(1):207.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Ježek J, Cooper KF, Strich R. Reactive oxygen species and mitochondrial dynamics: the yin and Yang of mitochondrial dysfunction and Cancer progression. Antioxidants (Basel, Switzerland). 2018;7(1):13.

    Google Scholar 

  60. Bernardo I, Bozinovski S, Vlahos R. Targeting oxidant-dependent mechanisms for the treatment of COPD and its comorbidities. Pharmacol Ther. 2015;155:60–79.

    Article  CAS  PubMed  Google Scholar 

  61. Marginean C, et al. Involvement of oxidative stress in COPD. Curr Health Sci J. 2018;44(1):48–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Domej W, Oettl K, Renner W. Oxidative stress and free radicals in COPD–implications and relevance for treatment. Int J Chron Obstruct Pulmon Dis. 2014;9:1207–24.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Schuliga M. NF-kappaB signaling in chronic inflammatory airway disease. Biomol Ther. 2015;5(3):1266–83.

    CAS  Google Scholar 

  64. Lingappan K. NF-κB in oxidative stress. Curr Opin Toxicol. 2018;7:81–6.

    Article  PubMed  Google Scholar 

  65. Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009;1(6):–a001651.

    Google Scholar 

  66. Bedard K, Krause K-H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87(1):245–313.

    Article  CAS  PubMed  Google Scholar 

  67. Frazziano G, Champion HC, Pagano PJ. NADPH oxidase-derived ROS and the regulation of pulmonary vessel tone. Am J Physiol Heart Circ Physiol. 2012;302(11):H2166–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Santillo M, et al. NOX signaling in molecular cardiovascular mechanisms involved in the blood pressure homeostasis. Front Physiol. 2015;6:194.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Klaus F, Rabe JRH, Suissa S. Cardiovascular disease and COPD: dangerous liaisons? Eur Respir Rev. 2018;27:180057.

    Article  Google Scholar 

  70. Guo X, et al. NOX4 expression and distal arteriolar remodeling correlate with pulmonary hypertension in COPD. BMC Pulm Med. 2018;18(1):111.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Pak O, et al. The effects of hypoxia on the cells of the pulmonary vasculature. Eur Respir J. 2007;30(2):364.

    Article  CAS  PubMed  Google Scholar 

  72. Veith C, et al. Molecular mechanisms of hypoxia-inducible factor-induced pulmonary arterial smooth muscle cell alterations in pulmonary hypertension. J Physiol. 2016;594(5):1167–77.

    Article  CAS  PubMed  Google Scholar 

  73. Waypa Gregory B, Chandel Navdeep S, Schumacker Paul T. Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing. Circ Res. 2001;88(12):1259–66.

    Article  Google Scholar 

  74. Veit F, et al. Hypoxia-dependent reactive oxygen species signaling in the pulmonary circulation: focus on ion channels. Antioxid Redox Signal. 2015;22(6):537–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Olschewski A, Weir EK. Redox regulation of ion channels in the pulmonary circulation. Antioxid Redox Signal. 2015;22(6):465–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012;48(2):158–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Costa RM, et al. H2O2 generated from mitochondrial electron transport chain in thoracic perivascular adipose tissue is crucial for modulation of vascular smooth muscle contraction. Vasc Pharmacol. 2016;84:28–37.

    Article  CAS  Google Scholar 

  78. Wang Z, et al. Rho-kinase activation is involved in hypoxia-induced pulmonary vasoconstriction. Am J Respir Cell Mol Biol. 2001;25(5):628–35.

    Article  CAS  PubMed  Google Scholar 

  79. Uehata M, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997;389(6654):990–4.

    Article  CAS  PubMed  Google Scholar 

  80. Barman SA, Zhu S, White RE. RhoA/Rho-kinase signaling: a therapeutic target in pulmonary hypertension. Vasc Health Risk Manag. 2009;5:663–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Barr J, et al. Nicotine induces oxidative stress and activates nuclear transcription factor kappa B in rat mesencephalic cells. Mol Cell Biochem. 2007;297(1–2):93–9.

    Article  CAS  PubMed  Google Scholar 

  82. Rao P, et al. Effects of cigarette smoke condensate on oxidative stress, apoptotic cell death, and HIV replication in human Monocytic cells. PLoS One. 2016;11(5):e0155791.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Hu F, et al. Ataxia-telangiectasia mutated (ATM) protein signaling participates in development of pulmonary arterial hypertension in rats. Med Sci Monit. 2017;23:4391–400.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Aoshiba K, et al. DNA damage as a molecular link in the pathogenesis of COPD in smokers. Eur Respir J. 2012;39(6):1368.

    Article  CAS  PubMed  Google Scholar 

  85. Gergalova G, et al. Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria. PLoS One. 2012;7(2):–e31361.

    Google Scholar 

  86. Lan X, et al. Nicotine induces podocyte apoptosis through increasing oxidative stress. PLoS One. 2016;11(12):e0167071.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Daijo H, et al. Cigarette smoke reversibly activates hypoxia-inducible factor 1 in a reactive oxygen species-dependent manner. Sci Rep. 2016;6:34424.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hill-Eubanks DC, et al. Calcium signaling in smooth muscle. Cold Spring Harb Perspect Biol. 2011;3(9):a004549.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Firth AL, Won JY, Park WS. Regulation of ca(2+) signaling in pulmonary hypertension. Korean J Physiol Pharmacol. 2013;17(1):1–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Yadav VR, et al. PLCγ1-PKCε-IP(3)R1 signaling plays an important role in hypoxia-induced calcium response in pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2018;314(5):L724–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Yadav VR, et al. Important role of PLC-γ1 in hypoxic increase in intracellular calcium in pulmonary arterial smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2013;304(3):L143–51.

    Article  CAS  PubMed  Google Scholar 

  92. Yang Z, et al. Important role of sarcoplasmic reticulum Ca2+ release via ryanodine receptor-2 channel in hypoxia-induced Rieske iron-sulfur protein-mediated mitochondrial ROS generation in pulmonary artery smooth muscle cells. Antioxid Redox Signal. 2020;32(7):447–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Nieves-Cintrón, M., et al., Regulation of voltage-gated potassium channels in vascular smooth muscle during hypertension and metabolic disorders. Microcirculation (New York, NY : 1994), 2018. 25(1): https://doi.org/10.1111/micc.12423.

  94. Pugliese SC, et al. The role of inflammation in hypoxic pulmonary hypertension: from cellular mechanisms to clinical phenotypes. Am J Physiol Lung Cell Mol Physiol. 2015;308(3):L229–52.

    Article  CAS  PubMed  Google Scholar 

  95. Perez-Zoghbi JF, et al. Ion channel regulation of intracellular calcium and airway smooth muscle function. Pulm Pharmacol Ther. 2009;22(5):388–97.

    Article  CAS  PubMed  Google Scholar 

  96. Ramirez GA, et al. Ion channels and transporters in inflammation: special focus on TRP channels and TRPC6. Cell. 2018;7(7):70.

    Article  CAS  Google Scholar 

  97. Wang Y-X, Zheng Y-M. ROS-dependent signaling mechanisms for hypoxic Ca(2+) responses in pulmonary artery myocytes. Antioxid Redox Signal. 2010;12(5):611–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Wang J, et al. Effects of chronic exposure to cigarette smoke on canonical transient receptor potential expression in rat pulmonary arterial smooth muscle. Am J Physiol Cell Physiol. 2014;306(4):C364–73.

    Article  CAS  PubMed  Google Scholar 

  99. Hong W, et al. Nicotine-induced airway smooth muscle cell proliferation involves TRPC6-dependent calcium influx via α7 nAChR. Cell Physiol Biochem. 2017;43(3):986–1002.

    Article  CAS  PubMed  Google Scholar 

  100. Lipskaia L, et al. Phosphatidylinositol 3-kinase and calcium-activated transcription pathways are required for VLDL-induced smooth muscle cell proliferation. Circ Res. 2003;92(10):1115–22.

    Article  CAS  PubMed  Google Scholar 

  101. Rokosova B, Peter Bentley J. Effect of calcium on cell proliferation and extracellular matrix synthesis in arterial smooth muscle cells and dermal fibroblasts. Exp Mol Pathol. 1986;44(3):307–17.

    Article  CAS  PubMed  Google Scholar 

  102. Lambert M, et al. Ion channels in pulmonary hypertension: a therapeutic interest? Int J Mol Sci. 2018;19(10):3162.

    Article  PubMed Central  CAS  Google Scholar 

  103. Song MY, Makino A, Yuan JXJ. Role of reactive oxygen species and redox in regulating the function of transient receptor potential channels. Antioxid Redox Signal. 2011;15(6):1549–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Liu T, Zhang L, Joo D, Sun S-C. NF-kB signaling in inflammation. Signal Transduct Target Ther. 2017;2:e17023)

    Google Scholar 

  105. Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. 2009;1(4):a000034.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Hayden MS, Ghosh S. NF-κB in immunobiology. Cell Res. 2011;21(2):223–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Matthews JR, et al. Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62. Nucleic Acids Res. 1992;20(15):3821–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Altamirano F, et al. Increased resting intracellular calcium modulates NF-κB-dependent inducible nitric-oxide synthase gene expression in dystrophic mdx skeletal myotubes. J Biol Chem. 2012;287(25):20876–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Lilienbaum A, Israël A. From calcium to NF-kappa B signaling pathways in neurons. Mol Cell Biol. 2003;23(8):2680–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Liu X, et al. T cell receptor-induced NF-KB signaling and transcriptional activation are regulated by STIM1- and Orai1-mediated calcium entry. J Biol Chem. 2016;291:8440–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Valdes JA, et al. NF-KB activation by depolarization of skeletal muscle cells depends on ryanodine and IP3 receptor-mediated calcium signals. Am J Phys Cell Phys. 2007;292:C1960–70.

    CAS  Google Scholar 

  112. D R, et al. High-frequency field stimulation of primary neurons enhances ryanodine receptor-mediated Ca2+ release and generates hydrogen peroxide, which jointly stimulate NF-κB activity. Antioxid Redox Signal. 2011;14(7):1245–59.

    Article  CAS  Google Scholar 

  113. Soon Bae J, et al. Phosphorylation of NF-κB by calmodulin-dependent kinase IV activates anti-apoptotic gene expression. Biochem Biophys Res Commun. 2003;305(4):1094–8.

    Article  CAS  Google Scholar 

  114. Kashiwase K, et al. CaMKII activates ASK1 and NF-κB to induce cardiomyocyte hypertrophy. Biochem Biophys Res Commun. 2005;327(1):136–42.

    Article  CAS  PubMed  Google Scholar 

  115. Stefano AD, et al. Increased expression of nuclear factor-kappaB in bronchial biopsies from smokers and patients with COPD. Eur Respir J. 2002;20:556–63.

    Article  PubMed  CAS  Google Scholar 

  116. Gagliardo R, et al. IkB kinase-driven nuclear factor-kB activation in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2011;128(3):635–645.e2.

    Article  CAS  PubMed  Google Scholar 

  117. Brown V, et al. Dysregulated apoptosis and NFkappaB expression in COPD subjects. Respir Res. 2009;10(1):24.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Raychaudhuri B, et al. Nitric oxide blocks nuclear factor-κB activation in alveolar macrophages. Am J Respir Cell Mol Biol. 1999;21(3):311–6.

    Article  CAS  PubMed  Google Scholar 

  119. Yang S-R, et al. RelB is differentially regulated by IkappaB kinase-alpha in B cells and mouse lung by cigarette smoke. Am J Respir Cell Mol Biol. 2009;40(2):147–58.

    Article  CAS  PubMed  Google Scholar 

  120. Tully JE, et al. Epithelial NF-κB orchestrates house dust mite-induced airway inflammation, hyperresponsiveness, and fibrotic remodeling. J Immunol. 2013;191(12):5811–21.

    Article  CAS  PubMed  Google Scholar 

  121. Price LC, et al. Nuclear factor κ-B is activated in the pulmonary vessels of patients with end-stage idiopathic pulmonary arterial hypertension. PLoS One. 2013;8(10):e75415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Hosokawa S, et al. Pathophysiological roles of nuclear factor kappaB (NF-kB) in pulmonary arterial hypertension: effects of synthetic selective NF-kB inhibitor IMD-0354. Cardiovasc Res. 2013;99(1):35–43.

    Article  CAS  PubMed  Google Scholar 

  123. Luo Y, et al. CD146-HIF-1α hypoxic reprogramming drives vascular remodeling and pulmonary arterial hypertension. Nat Commun. 2019;10(1):3551.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  124. Greijer AE, van der Wall E. The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. J Clin Pathol. 2004;57(10):1009–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Song T, Zheng Y-M, Wang Y-X. Cross talk between mitochondrial reactive oxygen species and sarcoplasmic reticulum calcium in pulmonary arterial smooth muscle cells. In: Wang Y-X, editor. Pulmonary vasculature redox signaling in health and disease. Cham: Springer International Publishing; 2017. p. 289–98.

    Chapter  Google Scholar 

  126. Hayden MS, West AP, Ghosh S. NF-kB and the immune response. Oncogene. 2006;25:6758–80.

    Article  CAS  PubMed  Google Scholar 

  127. Kimura S, et al. Nanoparticle-mediated delivery of nuclear factor κB decoy into lungs ameliorates Monocrotaline-induced pulmonary arterial hypertension. Hypertension. 2009;53(5):877–83.

    Article  CAS  PubMed  Google Scholar 

  128. Villegas L, Stidham T, Nozik-Grayck E. Oxidative stress and therapeutic development in lung diseases. J Pulmon Respirat Med. 2014;4(4):194.

    Article  Google Scholar 

  129. Feissner RF, et al. Crosstalk signaling between mitochondrial Ca2+ and ROS. Front Biosci (Landmark edition). 2009;14:1197–218.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA

    Lillian Truong, Yun-Min Zheng, Sharath Kandhi & Yong-Xiao Wang

Authors
  1. Lillian Truong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yun-Min Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sharath Kandhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yong-Xiao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Sharath Kandhi or Yong-Xiao Wang .

Editor information

Editors and Affiliations

  1. Department of Molecular & Cellular Physiology, Albany Medical College, Albany, NY, USA

    Yong-Xiao Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Truong, L., Zheng, YM., Kandhi, S., Wang, YX. (2021). Overview on Interactive Role of Inflammation, Reactive Oxygen Species, and Calcium Signaling in Asthma, COPD, and Pulmonary Hypertension. In: Wang, YX. (eds) Lung Inflammation in Health and Disease, Volume II. Advances in Experimental Medicine and Biology, vol 1304. Springer, Cham. https://doi.org/10.1007/978-3-030-68748-9_9

Download citation

Publish with us

Policies and ethics

Search

Navigation