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Sensing Environmental Factors: The Emerging Role of Receptors in Epidermal Homeostasis and Whole-Body Health

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Abstract

Epidermal keratinocytes have been recognized to form the water-impermeable structure and this barrier function is critical, especially for terrestrial animals. However, recent findings have dramatically changed the picture of epidermal keratinocytes, placing them at the forefront of the sensory system. Keratinocytes contains environmental sensors and a sensory information-processing system, and it generates a variety of hormones and neurotransmitters that influence whole-body states and emotions. Specifically, epidermal keratinocytes contain sensors of mechanical stress, temperature and chemical stimuli. Moreover, all the components of the hypothalamo-pituitary-adrenal (HPA) axis appear to be present in epidermal keratinocytes. These results suggest that the epidermis plays an important role in adapting whole-body physiology, and probably also emotional response, to changing environments.

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References

  • Arima M, Shimizu Y, Sowa J, Narita T, Nishi I, Iwata N, Ozaki N, Hashimoto S, Matsunaga K (2005) Psychosomatic analysis of atopic dermatitis using a psychological test. J Dermatol 32:160–168

    Article  PubMed  Google Scholar 

  • Ashida Y, Ogo M, Denda M (2001a) Epidermal IL-1 alpha generation is amplified at low humidities: Implications for the pathogenesis of inflammatory dermatoses. Br J Dermatol 144:238–243

    Article  CAS  PubMed  Google Scholar 

  • Ashida Y, Denda M, Hirao T (2001b) Histamine H1 and H2 receptor antagonists accelerate skin barrier repair and prevent epidermal hyperplasia induced by barrier disruption in a dry environment. J Invest Dermatol 116:261–265

    Article  CAS  PubMed  Google Scholar 

  • Capuron L, Miller AH (2011) Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther 130:226–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824

    Article  CAS  PubMed  Google Scholar 

  • Chung MK, Lee H, Caterina MJ (2003) Warm temperatures activate TRPV4 in mouse 308 keratinocytes. J Biol Chem 278:32037–32046

    Article  CAS  PubMed  Google Scholar 

  • Czeisler CA, Shanahan TL, Klerman EB, Martens H, Brotman DJ, Jonathan SE, Klein T, Rizzo JF (1995) Suppression of melatonin secretion in some blind patients by exposure to bright light. N Eng J Med 332:6–11

    Article  CAS  Google Scholar 

  • Denda M, Denda S (2007) Air-exposed keratinocytes exhibited intracellular oscillation. Skin Res Technol 13:195–201

    Article  PubMed  Google Scholar 

  • Denda M, Fuziwara S (2008) Visible radiation affects epidermal permeability barrier recovery: selective effects of red and blue light. J Invest Dermatol 128:1335–1336

    Article  CAS  PubMed  Google Scholar 

  • Denda M, Nakatani M (2010) Acceleration of permeability barrier recovery by exposure of skin to 10-30 kilohertz sound. Br J Dermatol 162:503–507

    Article  CAS  PubMed  Google Scholar 

  • Denda M, Tsutsumi M (2011) Roles of transient receptor potential proteins (TRPs) in epidermal keratinocytes transient receptor potential channels. Advan Exp Med Biol 704:847–860

    Article  CAS  Google Scholar 

  • Denda M, Tsutsumi M (2014) Possible role of epidermal keratinocytes in the construction of acupuncture meridians. J Acupunct Meridian Stud 7:92–94

    Article  PubMed  Google Scholar 

  • Denda M, Sato J, Masuda Y, Tsuchiya T, Koyama J, Kuramoto M, Elias PM, Feingold KR (1998a) Exposure to a dry environment enhances epidermal permeability barrier function. J Invest Dermatol 111:858–863

    Article  CAS  Google Scholar 

  • Denda M, Sato J, Tsuchiya T, Elias PM, Feingold KR (1998b) Low humidity stimulates epidermal DNA synthesis and amplifies the hyperproliferative response to barrier disruption: implication for seasonal exacerbations of inflammatory dermatoses. J Invest Dermatol 111:873–878

    Article  CAS  PubMed  Google Scholar 

  • Denda M, Fuziwara S, Inoue K, Denda S, Akamatsu H, Tomitaka A, Matsunaga K (2001) Immunoreactivity of VR1 on epidermal keratinocyte of human skin. Biochem Biophys Res Commun 285:1250–1252

    Article  CAS  PubMed  Google Scholar 

  • Denda M, Nakatani M, Ikeyama K, Tsutsumi M, Denda S (2007a) Epidermal keratinocytes as the forefront of the sensory system. Exp Dermatol 16:157–161

    Article  CAS  PubMed  Google Scholar 

  • Denda M, Sokabe T, Tominaga T, Tominaga M (2007b) Effects of skin surface temperature on epidermal permeability barrier homeostasis. J Invest Dermatol 127:654–659

    Article  CAS  PubMed  Google Scholar 

  • Denda M, Tsutsumi M, Goto M, Ikeyama K, Denda S (2010a) Topical application of TRPA1 agonists and brief cold exposure accelerate skin permeability barrier recovery. J Invest Dermatol 130:1942–1945

    Article  CAS  PubMed  Google Scholar 

  • Denda M, Tsutsumi M, Denda S (2010b) Topical application of TRPM8 agonists accelerates skin permeability barrier recovery and reduces epidermal proliferation induced by barrier insult: the role of cold-sensitive TRP receptors in epidermal permeability barrier homeostasis. Exp Dermatol 19:791–795

    Article  CAS  PubMed  Google Scholar 

  • Denda S, Takei K, Kumamoto J, Goto M, Tsutsumi M, Denda M (2012) Oxytocin is expressed in epidermal keratinocytes and released upon stimulation with adenosine 5’-[gamma-thio]triphosphate in vitro. Exp Dermatol 21:535–537

    Article  CAS  PubMed  Google Scholar 

  • Denda M, Takei K, Denda S (2013) How does epidermal pathology interact with mental state? Med Hypothesis 80:194–196

    Article  Google Scholar 

  • Dhaka A, Viswanath V, Patapoutian A (2006) TRP ion channels and temperature sensation. Ann Rev Neurosci 29:135–161

    Article  CAS  PubMed  Google Scholar 

  • Dhaka A, Uzzell V, Dubin AE, Mathur J, Petrus M, Bandell M, Patapoutian A (2009) TRPV1 is activated by both acidic and basic pH. J Neurosci 29:153–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferguson JN, Young LJ, Hearn EF (2000) Social amnesia in mice lacking the oxytocin gene. Nat Genet 25:284–288

    Article  CAS  PubMed  Google Scholar 

  • Fuziwara S, Inoue K, Denda M (2003) NMDA-type glutamate receptor is associated with cutaneous barrier homeostasis. J Invest Dermatol 120:1023–1029

    Article  CAS  PubMed  Google Scholar 

  • Fuziwara S, Suzuki A, Inoue K, Denda M (2005) Dopamine D2-like receptor agonists accelerate barrier repair and inhibit the epidermal hyperplasia induced by barrier disruption. J Invest Dermatol 125:783–789

    Article  CAS  PubMed  Google Scholar 

  • Gick B, Derrick D (2009) Aero-tactile integration in speech perception. Nature 462:502–504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goto M, Ikeyama K, Tsutsumi M, Denda S, Denda M (2010) Calcium ion propagation in cultured keratinocytes and other cells in skin in response to hydraulic pressure stimulation. J Cell Physiol 224:229–233

    CAS  PubMed  Google Scholar 

  • Goto M, Ikeyama K, Tsutsumi M, Denda S, Denda M (2011) Phosphodiesterase inhibitors block the acceleration of skin permeability barrier repair by red light. Exp Dermatol 20:568–571

    Article  CAS  PubMed  Google Scholar 

  • Hashiro M, Okumura M (1997) Anxiety, depression and psychosomatic symptoms in patients with atopic dermatitis: comparison with normal controls and among groups of different degrees of severity. J Dermatol Sci 14:63–67

    Article  CAS  PubMed  Google Scholar 

  • Heffner RS (2004) Primate hearing from a mammalian perspective. Anat Rec A Discov Mol Cell Evol Biol 281:1111–1122

    Article  PubMed  Google Scholar 

  • Hollander E, Notny S, Hanratty M (2003) Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology 28:193–198

    Article  CAS  PubMed  Google Scholar 

  • Hosoi J, Hariya T, Denda M, Tsuchiya T (2000) Regulation of the cutaneous allergic reaction by humidity. Contact Dermatitis 42:81–84

    Article  CAS  PubMed  Google Scholar 

  • Huang SM, Lee H, Chung MK et al (2008) Overexpressed transient receptor potential vanilloid 3 ion channels in skin keratinocytes modulate pain sensitivity via prostaglandin E2. J Neurosci 28:13727–13737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iijima T, Witter MP, Ichikawa M, Tominaga T, Kajiwara R, Matsumoto G (1996) Entorhinal-hippocampal interactions revealed by real-time imaging. Science 72:1176–1179

    Article  Google Scholar 

  • Ikeyama K, Fuziwara S, Denda M (2007) Topical application of neuronal nitric oxide synthase inhibitor accelerates cutaneous barrier recovery and prevents epidermal hyperplasia induced by barrier disruption. J Invest Dermatol 127:1713–1719

    Article  CAS  PubMed  Google Scholar 

  • Ikeyama K, Denda S, Tsutsumi M, Denda M (2010) Neuronal nitric oxide synthase in epidermis is involved in cutaneous circulatory response to mechanical stimulation. J Invest Dermatol 130:1158–1166

    Article  CAS  PubMed  Google Scholar 

  • Ikeyama K, Nakatani M, Kumamoto J, Denda M (2013) Distinct intracellular calcium responses of individual cultured human keratinocytes to air pressure changes. Skin Res Tech 19:346–351

    Article  Google Scholar 

  • Inoue K, Koizumi S, Fuziwara S, Denda S, Inoue K, Denda M (2002) Functional vanilloid receptors in cultured normal human keratinocytes. Biochem Biophys Res Commun 291:124–129

    Article  CAS  PubMed  Google Scholar 

  • Inoue K, Hosoi J, Denda M (2007) Extracellular ATP has stimulatory effects on the expression and release of IL-6 via purinergic receptors in normal human keratinocytes. J Invest Dermatol 127:362–371

    Article  CAS  PubMed  Google Scholar 

  • Katagiri C, Sato J, Nomura J, Denda M (2003) Changes in environmental humidity affect the water-holding property of the stratum corneum and its free amino acid content, and the expression of filaggrin in the epidermis of hairless mice. J Dermatol Sci 31:29–35

    Article  CAS  PubMed  Google Scholar 

  • Kawai N, Honda M, Nakamura S et al (2001) Catecholamines and opioid peptides increase in plasma in humans during possession trances. NeuroReport 12:3419–3423

    Article  CAS  PubMed  Google Scholar 

  • Kirsch P, Esslinger C, Chen Q (2005) Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci 25:11489–11493

    Article  CAS  PubMed  Google Scholar 

  • Liedtke W (2007) Role of TRPV ion channels in sensory transduction of osmotic stimuli in mammals. Exp Physiol 92:507–512

    Article  CAS  PubMed  Google Scholar 

  • Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65:732–741

    Article  CAS  PubMed  Google Scholar 

  • Nakatani M, Kawasoe T, Denda M (2011) Sex difference in human fingertip recognition of micron-level randomness as unpleasant. Int J Cosmet Sci 33:346–350

    Article  CAS  PubMed  Google Scholar 

  • Okano T, Yoshizawa T, Fukada Y (1994) Pinopsin is a chicken pineal photoreceptive molecule. Nature 372:94–97

    Article  CAS  PubMed  Google Scholar 

  • Oohashi T, Nishina E, Honda M et al (2000) Inaudible high-frequency sounds affect brain activity: hypersonic effect. J Neurophysiol 83:3548–3558

    CAS  PubMed  Google Scholar 

  • Oohashi T, Kawai N, Nishina E et al (2006) The role of biological system other than auditorair-conduction in the emergence of the hypersonic effect. Brain Res 1073–1074:339–347

    Article  PubMed  Google Scholar 

  • Pang Z, Sakamoto T, Tiwari V, Kim YS, Yang F, Dong X, Güler AD, Guan Y, Caterina MJ (2015) Selective keratinocyte stimulation is sufficient to evoke nociception in mice. Pain 156:656–665

    Article  CAS  PubMed  Google Scholar 

  • Peier AM, Moqrich A, Hergarden AC et al (2002a) A trp channel that senses cold stimuli and menthol. Cell 108:705–715

    Article  CAS  PubMed  Google Scholar 

  • Peier AM, Reeve AJ, Andersson DA, Moqrich A, Earley TJ, Hergarden AC, Story GM, Colley S, Hogenesch JB, McIntyre P, Bevan S, Patapoutian A (2002b) A heat-sensitive TRP channel expressed in keratinocytes. Science 296:2046–2049

    Article  CAS  PubMed  Google Scholar 

  • Pruszynski JA, Johansson RS (2014) Edge-orientation processing in first-order tactile neurons. Nat Neurosci 17:1404–1409

    Article  CAS  PubMed  Google Scholar 

  • Sapolsky RM (1996) Why stress is bad for your brain. Science 273:749–750

    Article  CAS  PubMed  Google Scholar 

  • Sato J, Yanai M, Hirao T, Denda M (2000) Water content and thickness of stratum corneum contribute to skin surface morphology. Arch Dermatol Res 292:412–417

    Article  CAS  PubMed  Google Scholar 

  • Sato J, Denda M, Chang S, Elias PM, Feingold KR (2002) Abrupt decreases in environmental humidity induce abnormalities in permeability barrier homeostasis. J Invest Dermatol 119:900–904

    Article  CAS  PubMed  Google Scholar 

  • Sauer GC, Hall JC (1996) Seasonal skin diseases. In: Sauer GC, Hall JC (eds) Manual of skin diseases. Lippincott-Raven, Philadelphia, pp 23–28

    Google Scholar 

  • Solessio E, Engbretson GA (1993) Antagonistic chromatic mechanisms in photoreceptors of the parietal eye of lizards. Nature 364:442–445

    Article  CAS  PubMed  Google Scholar 

  • Sorrells SF, Caso JR, Munhoz CD, Sapolsky RM (2009) The stressed CNS: when glucocorticoids aggravate inflammation. Neuron 64:33–39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Story GM, Peier AM, Reeve AJ et al (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112:819–829

    Article  CAS  PubMed  Google Scholar 

  • Takei K, Denda S, Kumamoto J, Denda M (2013) Low environmental humidity induces synthesis and release of cortisol in an epidermal organotypic culture system. Exp Dermatol 22:662–664

    Article  CAS  PubMed  Google Scholar 

  • Tsutsumi M, Ikeyama K, Denda S, Nakanishi J, Fuziwara S, Aoki H, Denda M (2009a) Expressions of rod and cone photoreceptor-like proteins in human epidermis. Exp Dermatol 18:567–570

    Article  CAS  PubMed  Google Scholar 

  • Tsutsumi M, Inoue K, Denda S, Ikeyama K, Goto M, Denda M (2009b) Mechanical-stimulation-evoked calcium waves in proliferating and differentiated human keratinocytes. Cell Tissue Res 338:99–106

    Article  CAS  PubMed  Google Scholar 

  • Tsutsumi M, Denda S, Ikeyama K, Goto M, Denda M (2010) Exposure to low temperature induces elevation of intracellular calcium in cultured human keratinocytes. J Invest Dermatol 130:1945–1948

    Article  CAS  PubMed  Google Scholar 

  • Tsutsumi M, Kumamoto J, Denda M (2011) Intracellular calcium response to high temperature is similar in undifferentiated and differentiated cultured human keratinocytes. Exp Dermatol 20:839–840

    Article  PubMed  Google Scholar 

  • Tsutsumi M, Goto M, Denda M (2013) Dynamics of intracellular calcium in cultured human keratinocytes after localized cell damage. Exp Dermatol 22:367–369

    Article  CAS  PubMed  Google Scholar 

  • Tyring S, Gottlieb A, Papp K, Gordon K, Leonardi C, Wang A, Lalla D, Woolley M, Jahreis A, Zitnik R, Cella D, Krishnan R (2006) Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 367:29–35

    Article  CAS  PubMed  Google Scholar 

  • Wilkinson JD, Rycroft RJ (1992) Contact dermatitis. In: Burton JL, Ebling FJG (eds) Textbook of dermatology, 5th edn. Blackwell Scientific Publications, Oxford, pp 614–615

    Google Scholar 

  • Wood LC, Jackson SM, Elias PM, Grunfeld C, Feingold KR (1992) Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. J Clin Invest 90:482–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yagi R, Nishina E, Honda M et al (2003) Modulatory effect of inaudible high-frequency sounds on human acoustic perception. Neurosci Lett 351:191–195

    Article  CAS  PubMed  Google Scholar 

  • Zhao X, Haeseleer F, Fariss RN, Huang J, Baehr W, Milam AH, Palczewski K (1997) Molecular cloning and localization of rhodopsin kinase in the mammalian pineal. Vis Neurosci 114:225–232

    Article  Google Scholar 

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Authors and Affiliations

  1. Japan Science and Technology Agency, CREST, Kawaguchi, Japan

    Mitsuhiro Denda

  2. Shiseido Research Center, Yokohama, Japan

    Mitsuhiro Denda

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Correspondence to Mitsuhiro Denda .

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  1. Department of Pharmacology and Toxicology, College of Pharmacy & The University of Arizona Cancer Center, Department of Pharmacology and Toxicology, TUCSON, Arizona, USA

    Georg T. Wondrak

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Denda, M. (2016). Sensing Environmental Factors: The Emerging Role of Receptors in Epidermal Homeostasis and Whole-Body Health. In: Wondrak, G. (eds) Skin Stress Response Pathways. Springer, Cham. https://doi.org/10.1007/978-3-319-43157-4_19

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