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IL‐10 inhibits inflammatory cytokines released by fetal mouse lung fibroblasts exposed to mechanical stretch
Author(s) -
Hawwa Renda L.,
Hokenson Michael A.,
Wang Yulian,
Huang Zheping,
Sharma Surendra,
SanchezEsteban Juan
Publication year - 2011
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.21433
Subject(s) - medicine , proinflammatory cytokine , fetus , lung , immunology , inflammatory response , inflammation , pregnancy , biology , genetics
Background Mechanical ventilation plays an important role in the pathogenesis of bronchopulmonary dysplasia. However, the molecular mechanisms by which excessive stretch induces lung inflammation are not well characterized. Objectives In this study, we investigated in vitro the contribution of lung mesenchymal cells to the inflammatory response mediated by mechanical stretch and the potential protective role of IL‐10. Methods Fetal mouse lung fibroblasts isolated during the saccular stage of lung development were exposed to 20% cyclic stretch to simulate mechanical injury. The phenotype of cultured fibroblasts was investigated by red oil O and alpha‐smooth muscle actin (α‐SMA) staining. Cell necrosis, apoptosis, and inflammation were analyzed by lactate dehydrogenase release, cleaved caspase‐3 activation and release of cytokines and chemokines into the supernatant, respectively. Results First, we characterized the phenotype of the cultured fibroblasts and found an absence of red oil O staining and 100% positive staining for α‐SMA, indicating that cultured fibroblasts were myofibroblasts. Mechanical stretch increased necrosis and apoptosis by two‐ and three‐fold, compared to unstretched samples. Incubation of monolayers with IL‐10 prior to stretch did not affect necrosis but significantly decreased apoptosis. Mechanical stretch increased release of pro‐inflammatory cytokines and chemokines IL‐1β, MCP‐1, RANTES, IL‐6, KC and TNF‐α into the supernatant by 1.5‐ to 2.5‐fold, and administration of IL‐10 before stretch blocked that release. Conclusions Our data demonstrate that lung interstitial cells may play a significant role in the inflammatory cascade triggered by mechanical stretch. IL‐10 protects fetal fibroblasts from injury secondary to stretch. Pediatr. Pulmonol. 2011; 46:640–649. © 2011 Wiley‐Liss, Inc.