Skip to main content
SpringerLink
Log in

Intranasal administration with recombinant Lactococcus lactis expressing heme oxygenase-1 reduces hyperoxia-induced lung inflammation in rat pups

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Objectives

To evaluate the effects of a recombinant strain of Lactococcus lactis secreting bioactive heme oxygenase-1 (LL-HO-1) in a model of hyperoxia-induced lung injury in rat pups

Results

Intranasal administration with LL-HO-1 significantly reduced hyperoxia-induced lung injury as demonstrated by a decreased wet/dry ratio, myeloperoxidase activity in lung tissue, tumor necrosis factor alpha levels in bronchoalveolar lavage (BAL) fluid, and attenuated lung injury scores. Although expression of HO-1 and NADPH oxidase-1 and production of superoxide in lung tissue were not affected by LL-HO-1 treatment, HO-1 levels in nasal mucosa and interleukin-10 concentrations in BAL fluid significantly increased compared with the hyperoxia control group

Conclusions

Intranasal administration of LL-HO-1 protects against hyperoxia-induced lung damage, apparently through attenuation of inflammation.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Ahmed MN, Suliman HB, Folz RJ, Nozik-Grayck E, GolsonML Mason SN, Auten RL (2003) Extracellular superoxide dismutase protects lung development in hyperoxia-exposed newborn mice. Am J Respir Crit Care Med 167:400–405

    Article  PubMed  Google Scholar 

  • Ajuebor MN, Das AM, Virag L, Flower RJ, Szabo C, Perretti M (1999) Role of resident peritoneal macrophages and mast cells in chemokine production and neutrophil migration in acute inflammation: evidence for an inhibitory loop involving endogenous IL-10. J Immunol 162:1685–1691

    CAS  PubMed  Google Scholar 

  • Bermudez-Humaran LG, Aubry C, Motta JP, Deraison C, Steidler L, Vergnolle N, Chatel JM, Langella P (2013) Engineering lactococci and lactobacilli for human health. Curr Opin Microbiol 16:278–283

    Article  CAS  PubMed  Google Scholar 

  • Bhandari V, Elias JA (2006) Cytokines in tolerance to hyperoxia-induced injury in the developing and adult lung. Free Radic Biol Med 41:4–18

    Article  CAS  PubMed  Google Scholar 

  • Carnesecchi S, Deffert C, Pagano A, Garrido-Urbani S, Metrailler-Ruchonnet I, Schappi M, Donati Y, Matthay MA, Krause KH, Barazzone Arqiroffo C (2009) NADPH oxidase-1 plays a crucial role in hyperoxia-induced acute lung injury in mice. Am J Respir Crit Care Med 180:972–981

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Chen HI, Yeh DY, Liou HL, Kao SJ (2006) Insulin attenuates endotoxin-induced acute lung injury in conscious rats. Crit Care Med 34:758–764

    Article  CAS  PubMed  Google Scholar 

  • Donnelly LE, Barnes PJ (2001) Expression of heme oxygenase in human airway epithelial cells. Am J Respir Cell Mol Biol 24:295–303

    Article  CAS  PubMed  Google Scholar 

  • Frank L (1991) Developmental aspects of experimental pulmonary oxygen-toxicity. Free Rad Biol Med 11:463–494

    Article  CAS  PubMed  Google Scholar 

  • Griendling KK, Ushio-Fukai M (2000) Reactive oxygen species as mediators of angiotensin II signaling. Regul Pept 91:21–27

    Article  CAS  PubMed  Google Scholar 

  • Ho YS, Vincent R, Dey MS, Slot JW, Crapo JD (1998) Transgenic models for the study of lung antioxidant defense: enhanced manganese-containing superoxide dismutase activity gives partial protection to B6C3 hybrid mice exposed to hyperoxia. Am J Respir Cell Mol Biol 18:538–547

    Article  CAS  PubMed  Google Scholar 

  • Jensen JC, Pogrebniak HW, Pass HI, Buresh C, Merino MJ, Kauffman D, Venzon D, Langstein HN, Norton JA (1992) Role of tumor necrosis factor in oxygen toxicity. J Appl Physiol 72:1902–1907

    CAS  PubMed  Google Scholar 

  • Johnston CJ, Wright TW, Reed CK, Finkelstein JN (1997) Comparison of adult and newborn pulmonary cytokine mRNA expression after hyperoxia. Exp Lung Res 23:537–552

    Article  CAS  PubMed  Google Scholar 

  • Lambeth JD (2004) NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4:181–189

    Article  CAS  PubMed  Google Scholar 

  • Lee PJ, Alam J, Wiegand GW, Choi AM (1996) Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia. Proc Natl Acad Sci U S A 93:10393–10398

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Li J, Gao X, Qian M, Eaton JW (2004) Mitochondrial metabolism underlies hyperoxic cell damage. Free Radic Biol Med 36:1460–1470

    Article  CAS  PubMed  Google Scholar 

  • Li N, Russell WM, Douglas-Escobar M, Hauser N, Lopez M, Neu J (2009) Live and heat-killed Lactobacillus rhamnosus GG: effects on proinflammatory and anti-inflammatory cytokines/chemokines in gastrostomy-fed infant rats. Pediatr Res 66:203–207

    Article  CAS  PubMed  Google Scholar 

  • Otterbein LE, Kolls JK, Mantell LL, Cook JL, Alam J, Choi AM (1999) Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury. J Clin Invest 103:1047–1054

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Otterbein LE, Bach FH, Alam J, Soares M, Tao LH, Wysk M, Davis RJ, Flavell RA, Choi AM (2000) Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6:422–428

    Article  CAS  PubMed  Google Scholar 

  • Otterbein LE, Otterbein SL, Ifedigbo E, Liu F, Morse DE, Fearns C, Ulevitch RJ, Knickelbein R, Flavell RA, Choi AM (2003) MKK3 mitogen-activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury. Am J Pathol 163:2555–2563

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pae HO, Oh GS, Choi BM, Chae SC, Kim YM, Chung KR, Chung HT (2004) Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production. J Immunol 172:4744–4751

    Article  CAS  PubMed  Google Scholar 

  • Pang QF, Ji Y, Li Y, Bermudez-Humaran LG, Hu G, Zeng YM (2008) Intragastric administration with recombinant Lactococcus lactis producing heme oxygenase-1 prevents lipopolysaccharide-induced endotoxemia in rats. FEMS Microbiol Lett 283:62–68

    Article  CAS  PubMed  Google Scholar 

  • Pang QF, Ji Y, Bermudez-Humaran LG, Zhou QM, Hu G, Zeng YM (2009) Protective effects of a Heme Oxygenase-1-Secreting Lactococcus lactis on mucosal injury induced by hemorrhagic shock in rats. J Surg Res 153:39–45

    Article  CAS  PubMed  Google Scholar 

  • Shasby DM, Fox RB, Harada RN, Repine JE (1982) Reduction of the edema of acute hyperoxic lung injury by granulocyte depletion. J Appl Physiol 52:1237–1244

    CAS  PubMed  Google Scholar 

  • Shea LM, Beehler C, Schwartz M, Shenkar R, Tuder R, Abraham E (1996) Hyperoxia activates NF-kappaB and increases TNF-alpha and IFN-gamma gene expression in mouse pulmonary lymphocytes. J Immunol 157:3902–3908

    CAS  PubMed  Google Scholar 

  • Sorescu D, Weiss D, Lassegue B, Clempus RE, Szocs K, Sorescu GP, Valppu L, Quinn MT, Lambeth JD, Vega JD, TaylorWR Griendling KK (2002) Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation 105:1429–1435

    Article  CAS  PubMed  Google Scholar 

  • Taylor JL, Carraway MS, Piantadosi CA (1998) Lung-specific induction of heme oxygenase-1 and hyperoxic lung injury. Am J Physiol 274:L582–L590

    CAS  PubMed  Google Scholar 

  • Van Marter LJ (2009) Epidemiology of bronchopulmonary dysplasia. Semin Fetal Neonatal Med 14:358–366

    Article  PubMed  Google Scholar 

  • Wu CY, Zeng YM, Pang QF (2006) Cloning and expression of rat heme oxygenase-1 gene in Lactococcus lactis. Chin J Appl Environ Biol 12:48–51

    CAS  Google Scholar 

  • Yusa T, Crapo JD, Freeman BA (1984) Hyperoxia enhances lung and liver nuclear superoxide generation. Biochim Biophys Acta 798:167–174

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by the National Natural Science Foundation of China (No. 30801075).

Conflict of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, China

    Chang-Yi Wu, Feng Yue, Min Li & Li-Ping Zhang

  2. INRA, UMR1319 Micalis, 78350, Jouy-en-Josas, France

    Luis G. Bermúdez-Humarán

  3. UMR Micalis, AgroParisTech, 78350, Jouy-en-Josas, France

    Luis G. Bermúdez-Humarán

Authors
  1. Chang-Yi Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luis G. Bermúdez-Humarán
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Feng Yue
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Min Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li-Ping Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chang-Yi Wu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, CY., Bermúdez-Humarán, L.G., Yue, F. et al. Intranasal administration with recombinant Lactococcus lactis expressing heme oxygenase-1 reduces hyperoxia-induced lung inflammation in rat pups. Biotechnol Lett 37, 1203–1211 (2015). https://doi.org/10.1007/s10529-015-1795-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-015-1795-3

Keywords

Search

Navigation