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Src tyrosine kinases mediate activations of NF-kappa B and integrin signal during lipopolysaccharide-induced acute lung injury

Title
Src tyrosine kinases mediate activations of NF-kappa B and integrin signal during lipopolysaccharide-induced acute lung injury
Authors
Lee, Hui S.Moon, ChafigsukLee, Hye W.Park, Eun-MiCho, Min-SunKang, Jihee L.
Ewha Authors
이지희조민선박은미
SCOPUS Author ID
이지희scopus; 조민선scopus; 박은미scopus
Issue Date
2007
Journal Title
JOURNAL OF IMMUNOLOGY
ISSN
0022-1767JCR Link
Citation
vol. 179, no. 10, pp. 7001 - 7011
Publisher
AMER ASSOC IMMUNOLOGISTS
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Src tyrosine kinases (TKs) are signaling proteins involved in cell signaling pathways toward cytoskeletal, membrane and nuclear targets. In the present study, using a selective Src TK inhibitor, PP1, we investigated the roles of Src TKs in the key pulmonary responses, NF-kappa B activation, and integrin signaling during acute lung injury in BALB/C mice intratracheally treated with LPS. LPS resulted in c-Src phosphorylation in lung tissue and the phospho-c-Src was predominantly localized in recruited neutrophils and alveolar macrophages. PP1 inhibited LPS-induced increases in total protein content in bronchoalveolar lavage fluid, neutrophil recruitment, and increases in the production or activity of TNF-alpha and matrix metalloproteinase-9. PP1 also blocked LPS-induced NF-alpha B activation, and phosphorylation and degradation of I kappa B-alpha. The inhibition of NF-kappa B activation by PP1 correlated with a depression of LPS-induced integrin signaling, which included increases in the phosphorylations of integrin 03, and of the focal adhesion kinase (FAK) family members, FAK and Pyk2, in lung tissue, and reductions in the fibrinogen-binding activity of alveolar macrophages. Moreover, treatment with anti-alpha(v), anti-beta(3), or Arg-Gly-Asp-Ser (RGDS), inhibited LPS-induced NF-kappa B activation. Taken together, our findings suggest that Src TKs play a critical role in LPS-induced activations of NF-kappa B and integrin (alpha(v)beta(3)) signaling during acute lung injury. Therefore, Src TK inhibition may provide a potential means of ameliorating inflammatory cascade-associated lung injury.
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의과대학 > 의학과 > Journal papers
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