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

• Published in: Respiratory research 2009-03, Vol.10 (18), p.18-18, Article 18
• Main Authors: Moon, Changsuk, Han, Jeong Ran, Park, Hyun-Jung, Hah, Jong Sik, Kang, Jihee Lee
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - enzymology; Acute Lung Injury - immunology; Acute Lung Injury - prevention & control; Acute respiratory distress syndrome; Animals; Bronchoalveolar Lavage Fluid - immunology; Care and treatment; Chemokine CXCL2 - metabolism; Chemotaxis - drug effects; Development and progression; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases - metabolism; Focal Adhesion Kinase 1 - metabolism; Health aspects; Inflammation; Inflammation Mediators - metabolism; Integrin alphaVbeta3 - metabolism; Integrins; JNK Mitogen-Activated Protein Kinases - metabolism; Lipopolysaccharides; Lung - drug effects; Lung - enzymology; Lung - immunology; Macrophages - drug effects; Macrophages - immunology; Male; MAP Kinase Signaling System - drug effects; Matrix Metalloproteinase 9 - metabolism; Mice; Mice, Inbred BALB C; Neutrophil Infiltration - drug effects; Oligopeptides - pharmacology; p38 Mitogen-Activated Protein Kinases - metabolism; Peptides; Phosphorylation; Phosphotransferases; Physiological aspects; Pneumonia - chemically induced; Pneumonia - enzymology; Pneumonia - immunology; Pneumonia - prevention & control; Prevention; Time Factors; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1465-993X; 1465-9921; 1465-993X
• DOI: 10.1186/1465-9921-10-18

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. 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-alphav or anti-beta3 mAb (5 mg/kg, i.p.). Mice were sacrificed 4 or 24 h post-LPS. A pretreatment with RGDS inhibited LPS-induced increases in neutrophil and macrophage numbers, total protein levels and TNF-alpha 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 alphav significantly 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-beta3 also inhibited all LPS-induced inflammatory responses, except the accumulation of BAL protein at 24 h post-LPS. These results suggest that RGDS with high specificity for alphavintegrins attenuates inflammatory cascade during LPS-induced development of acute lung injury.