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Pediatr Pulmonol. 2011 Jul;46(7):640-9. doi: 10.1002/ppul.21433. Epub 2011 Feb 18.

IL-10 inhibits inflammatory cytokines released by fetal mouse lung fibroblasts exposed to mechanical stretch.

Author information

  • 1Department of Pediatrics, Women and Infants Hospital of Rhode Island, 101 Dudley Street, Providence, Rhode Island 02905, USA.

Abstract

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.

Copyright © 2011 Wiley-Liss, Inc.

PMID:
21337733
[PubMed - indexed for MEDLINE]
PMCID:
PMC3103753
Free PMC Article

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