Research

Role of TNF-α in lung tight junction alteration in mouse model of acute lung inflammation

Emanuela Mazzon¹ and Salvatore Cuzzocrea^1,2

¹  IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy

²  Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy

author email corresponding author email

Respiratory Research 2007, 8:75doi:10.1186/1465-9921-8-75

Published:	30 October 2007

Abstract

In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-αR1KO) to understand the roles of TNF-α on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-α inhibition significantly reduced the degree of (1) TNF-α production in pleural exudates and in the lung tissues, (2) the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity), (3) the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and β-catenin (immunohistochemistry) and (4) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-α on lung barrier dysfunction.