Overexpression of Stat3C in pulmonary epithelium protects against hyperoxic lung injury

Xuemei Lian, Yulin Qin, Shaikh Abu Hossain, Li Yang, Amanda White, Huan Xu, J. Michael Shipley, Tingyu Li, Robert M. Senior, Hong Du, Cong Yan

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Acute lung injury is a side effect of therapy with a high concentration of inspired oxygen in patients. The molecular mechanism underlining this effect is poorly understood. In this study, we report that overexpression of Stat3C, a constitutive active form of STAT3, in respiratory epithelial cells of a doxycycline-controlled double-transgenic mouse system protects lung from inflammation and injury caused by hyperoxia. In this mouse line, >50% of transgenic mice survived exposure to 95% oxygen at day 7, compared with 0% survival of wild-type mice. Overexpression of STAT3C delays acute capillary leakage and neutrophil infiltration into the alveolar region. This protection is mediated at least partially through inhibition of hyperoxia-induced synthesis and release of matrix metalloproteinase (MMP)-9 and MMP-12 by neutrophils and alveolar resident cells. In some MMP-9-/- mice, prolonged survival was observed under hyperoxic condition. The finding supports a concept that activation of the Stat3 pathway plays a role to prevent hyperoxia-induced inflammation and injury in the lung.

Original languageEnglish (US)
Pages (from-to)7250-7256
Number of pages7
JournalJournal of Immunology
Volume174
Issue number11
StatePublished - Jun 1 2005
Externally publishedYes

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Hyperoxia
Lung Injury
Epithelium
Matrix Metalloproteinase 9
Lung
Transgenic Mice
Matrix Metalloproteinase 12
Oxygen
Alveolar Epithelial Cells
Neutrophil Infiltration
Acute Lung Injury
Doxycycline
Pneumonia
Neutrophils
Epithelial Cells
Inflammation
Survival
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Lian, X., Qin, Y., Hossain, S. A., Yang, L., White, A., Xu, H., ... Yan, C. (2005). Overexpression of Stat3C in pulmonary epithelium protects against hyperoxic lung injury. Journal of Immunology, 174(11), 7250-7256.

Overexpression of Stat3C in pulmonary epithelium protects against hyperoxic lung injury. / Lian, Xuemei; Qin, Yulin; Hossain, Shaikh Abu; Yang, Li; White, Amanda; Xu, Huan; Shipley, J. Michael; Li, Tingyu; Senior, Robert M.; Du, Hong; Yan, Cong.

In: Journal of Immunology, Vol. 174, No. 11, 01.06.2005, p. 7250-7256.

Research output: Contribution to journalArticle

Lian, X, Qin, Y, Hossain, SA, Yang, L, White, A, Xu, H, Shipley, JM, Li, T, Senior, RM, Du, H & Yan, C 2005, 'Overexpression of Stat3C in pulmonary epithelium protects against hyperoxic lung injury', Journal of Immunology, vol. 174, no. 11, pp. 7250-7256.
Lian X, Qin Y, Hossain SA, Yang L, White A, Xu H et al. Overexpression of Stat3C in pulmonary epithelium protects against hyperoxic lung injury. Journal of Immunology. 2005 Jun 1;174(11):7250-7256.
Lian, Xuemei ; Qin, Yulin ; Hossain, Shaikh Abu ; Yang, Li ; White, Amanda ; Xu, Huan ; Shipley, J. Michael ; Li, Tingyu ; Senior, Robert M. ; Du, Hong ; Yan, Cong. / Overexpression of Stat3C in pulmonary epithelium protects against hyperoxic lung injury. In: Journal of Immunology. 2005 ; Vol. 174, No. 11. pp. 7250-7256.
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