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Mechanical stretch has contrasting effects on mediator release from bronchial epithelial cells, with a rho-kinase-dependent component to the mechanotransduction pathway.

Abstract：

INTRODUCTION:In vivo, the airway epithelium stretches and relaxes with each respiratory cycle, but little is known about the effect this pattern of elongation and relaxation has on bronchial epithelial cells. We have used a model of cell deformation to measure the effect of stretch on inflammatory cytokine release by the BEAS 2B cell line, and to examine the method of mechanotransduction in these cells. METHODS:BEAS 2B cells were cyclically stretched using the Flexercell system. IL-8 and RANTES protein and RNA levels were measured after different elongations, rates and duration of stretch. An inhibitor of Rho (Ras Homologous)-associated kinases was used, to assess the effect of blocking downstream of integrin signalling. Immunofluorescent staining of paxillin was used to study the effect of stretch on the distribution of focal contacts and the organisation of the actin cytoskeleton. RESULTS:IL-8 release by BEAS 2B cells was increased by cytokine stimulation and stretch, whereas RANTES levels in the cell supernatant decreased after stretch in a dose-, time- and rate-dependent manner. Thirty percent elongation at 20 cycles/min for 24h increased IL-8 levels by over 100% (P < 0.01). Blocking rho kinase using Y-27632 inhibited the effect of stretch on IL-8 release by the BEAS 2B cells. Immunofluorescent staining demonstrated that stretch caused dramatic disassembly of focal adhesions and resulted in the redistribution of paxillin to the peri-nuclear region. CONCLUSION:This study demonstrates a marked effect of stretch on bronchial epithelial cell function. We propose that stretch modulates epithelial cell function via the activation of rho kinases. The observation that stretch promotes focal adhesion disassembly suggests a mechanism whereby focal adhesion turnover (coordination of assembly and disassembly) is essential for mechanotransduction in bronchial epithelial cells.

journal_name

Respir Med

journal_title

Respiratory medicine

authors

Thomas RA,Norman JC,Huynh TT,Williams B,Bolton SJ,Wardlaw AJ

doi

10.1016/j.rmed.2005.12.008

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

1588-97

issue

eissn

0954-6111

issn

1532-3064

pii

S0954-6111(05)00553-6

journal_volume

100

pub_type

杂志文章

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Mechanical stretch has contrasting effects on mediator release from bronchial epithelial cells, with a rho-kinase-dependent component to the mechanotransduction pathway.