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Toll‐like receptor 2 signaling pathway in lung injury
Author(s) -
Jezierska Agnieszka,
Kolosova Irina A,
Verin Alexander D
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.952.6
Subject(s) - microbiology and biotechnology , tlr2 , ards , mapk/erk pathway , signal transduction , phosphorylation , stress fiber , inflammation , myosin light chain kinase , toll like receptor , receptor , medicine , chemistry , immunology , cancer research , lung , biology , innate immune system , tlr4 , focal adhesion
Endothelial cell (EC) barrier is critical for regulation of fluids and gas exchange through an alveolar space. Disruption of this barrier leads to pulmonary edema and lung inflammation [hallmarks of acute lung injury (ALI)], often followed by multi‐organ failure or even death. Based on data of literature, we hypothesize that in development of this pathological conditions Toll‐like receptor 2 (TLR2) signaling is involved. To test this hypothesis we employed several methods including measurements of transendothelial electrical resistance, fluorescent imaging and western blotting. Our data demonstrate that TLR2 specific agonist, Zymosan and TLR2 specific antibody activate pro‐contractile pathways including increased in myosin light chain (MLC) phosphorylation, p38 and ERK MAPK activation, leading to increase in actin stress fibers, gap formation and EC permeability increase. This was accompanied by active beta‐catenins liberation from endothelial junctional complexes with VE‐cadherin. Based on our data, we strongly believe that targeting and inhibiting TLR2 or TLR2 related proteins with specific agonists may benefit patients with ALI or even more severe form acute respiratory distress syndrome (ARDS).