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Interaction of cyclic mechanical stretch and toll‐like receptor 4‐mediated innate immunity in rat alveolar type II cells
Author(s) -
Kuhn Hartmut,
Petzold Katja,
Hammerschmidt Stefan,
Wirtz Hubert
Publication year - 2014
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/resp.12149
Subject(s) - innate immune system , medicine , immunity , toll like receptor , receptor , microbiology and biotechnology , immunology , toll , immune system , biology
Background and objective In cases of infection‐induced acute lung injury, mechanical ventilation might be necessary to maintain oxygenation. Although low tidal volume ventilation is applied, alveolar over‐distension may occur and result in ventilator‐induced lung injury. In this study, we investigate (i) the influence of lipopolysaccharide ( LPS ) stimulation on high‐amplitude stretching; and (ii) the effect of stretching on LPS ‐mediated immune response in isolated rat alveolar type II cells. Methods Type II cells were incubated with LPS and stretched for 24 h on elastic membranes. Initially we examined apoptosis and lactic acid dehydrogenase release in LPS ‐treated stretched cells. Furthermore we determined toll‐like receptor ( TLR ) 4 expression, TLR 4 signalling by analysis of nuclear factor κB ( NF‐κB ) activation and the secretion of inflammatory cytokines (monocyte chemoattractant protein‐1, macrophage inflammatory protein‐2, interleukin‐1 beta, tumour necrosis factor alpha). Results Our results show that LPS increases apoptosis and cytotoxicity in high amplitude stretched cells. Stretching and LPS activate NF‐κB . The LPS influence is the prevailing one while no synergistic effects were observed by additional stretching. LPS stimulates an increased secretion of the inflammatory mediators only. Stretching had no influence on cytokines secretion. Conclusions We conclude that activation of TLR4 mediated immunity intensifies cell damage caused by stretching whereas in return stretching had no influence on TLR4 mediated innate immunity.