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Synthetic RGDS peptide attenuates lipopolysaccharide-induced pulmonary inflammation by inhibiting integrin signaled MAP kinase pathways

Title
Synthetic RGDS peptide attenuates lipopolysaccharide-induced pulmonary inflammation by inhibiting integrin signaled MAP kinase pathways
Authors
Moon C.Han J.R.Park H.-J.Hah J.S.Kang J.L.
Ewha Authors
하종식이지희
SCOPUS Author ID
하종식scopus; 이지희scopus
Issue Date
2009
Journal Title
Respiratory Research
ISSN
1465-9921JCR Link
Citation
vol. 10
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Background: Synthetic peptides containing the RGD sequence inhibit integrin-related functions in different cell systems. Here, we investigated the effects of synthetic Arg-Gly-Asp-Ser (RGDS) peptide on key inflammatory responses to intratracheal (i.t.) lipopolysaccharide (LPS) treatment and on the integrin signaled mitogen-activated protein (MAP) kinase pathway during the development of acute lung injury.Methods: Saline or LPS (1.5 mg/kg) was administered i.t. with or without a single dose of RGDS (1, 2.5, or 5 mg/kg, i.p.), anti-αvor anti-β3mAb (5 mg/kg, i.p.). Mice were sacrificed 4 or 24 h post-LPS.Results: A pretreatment with RGDS inhibited LPS-induced increases in neutrophil and macrophage numbers, total protein levels and TNF-α and MIP-2 levels, and matrix metalloproteinase-9 activity in bronchoalveolar lavage (BAL) fluid at 4 or 24 h post-LPS treatment. RGDS inhibited LPS-induced phosphorylation of focal adhesion kinase and MAP kinases, including ERK, JNK, and p38 MAP kinase, in lung tissue. Importantly, the inhibition of the inflammatory responses and the kinase pathways were still evident when this peptide was administered 2 h after LPS treatment. Similarly, a blocking antibody against integrin αvsignificantly inhibited LPS-induced inflammatory cell migration into the lung, protein accumulation and proinflammatory mediator production in BAL fluid, at 4 or 24 h post-LPS. Anti-β3also inhibited all LPS-induced inflammatory responses, except the accumulation of BAL protein at 24 h post-LPS.Conclusion: These results suggest that RGDS with high specificity for αvintegrins attenuates inflammatory cascade during LPS-induced development of acute lung injury. © 2009 Moon et al; licensee BioMed Central Ltd.
DOI
10.1186/1465-9921-10-18
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의학전문대학원 > 의학과 > Journal papers
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