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

Moon C, Han JR, Park HJ, Hah JS, Kang JL - Respir. Res. (2009)

Bottom Line: RGDS inhibited LPS-induced phosphorylation of focal adhesion kinase and MAP kinases, including ERK, JNK, and p38 MAP kinase, in lung tissue.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.These results suggest that RGDS with high specificity for alphavintegrins attenuates inflammatory cascade during LPS-induced development of acute lung injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Division of Cell Biology, Ewha Medical Research Center, School of Medicine, Ewha Womans University, Seoul, Seoul, Korea. 94cmoon@hanmail.net

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-alphav or anti-beta3 mAb (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-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.

Conclusion: These results suggest that RGDS with high specificity for alphavintegrins attenuates inflammatory cascade during LPS-induced development of acute lung injury.

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Related in: MedlinePlus

Reduction in LPS-induced lung inflammation by RGDS. Mice were administered RGDS (5 mg/kg, i.p.) once 1 h before or 2 h after LPS and were sacrificed 24 h post-LPS. Lung sections were H&E stained, as described in Methods. Representative staining from 5 mice per group are shown.
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Figure 2: Reduction in LPS-induced lung inflammation by RGDS. Mice were administered RGDS (5 mg/kg, i.p.) once 1 h before or 2 h after LPS and were sacrificed 24 h post-LPS. Lung sections were H&E stained, as described in Methods. Representative staining from 5 mice per group are shown.

Mentions: Histological lung sections obtained 24 h post-LPS confirmed BAL findings. H&E sections of lungs fixed with paraformaldehyde revealed similar reductions in peribroncheal and intraalveolar infiltration of neutrophils in lungs treated with RGDS at different times (Figure 2).


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

Moon C, Han JR, Park HJ, Hah JS, Kang JL - Respir. Res. (2009)

Reduction in LPS-induced lung inflammation by RGDS. Mice were administered RGDS (5 mg/kg, i.p.) once 1 h before or 2 h after LPS and were sacrificed 24 h post-LPS. Lung sections were H&E stained, as described in Methods. Representative staining from 5 mice per group are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666640&req=5

Figure 2: Reduction in LPS-induced lung inflammation by RGDS. Mice were administered RGDS (5 mg/kg, i.p.) once 1 h before or 2 h after LPS and were sacrificed 24 h post-LPS. Lung sections were H&E stained, as described in Methods. Representative staining from 5 mice per group are shown.
Mentions: Histological lung sections obtained 24 h post-LPS confirmed BAL findings. H&E sections of lungs fixed with paraformaldehyde revealed similar reductions in peribroncheal and intraalveolar infiltration of neutrophils in lungs treated with RGDS at different times (Figure 2).

Bottom Line: RGDS inhibited LPS-induced phosphorylation of focal adhesion kinase and MAP kinases, including ERK, JNK, and p38 MAP kinase, in lung tissue.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.These results suggest that RGDS with high specificity for alphavintegrins attenuates inflammatory cascade during LPS-induced development of acute lung injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Division of Cell Biology, Ewha Medical Research Center, School of Medicine, Ewha Womans University, Seoul, Seoul, Korea. 94cmoon@hanmail.net

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-alphav or anti-beta3 mAb (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-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.

Conclusion: These results suggest that RGDS with high specificity for alphavintegrins attenuates inflammatory cascade during LPS-induced development of acute lung injury.

Show MeSH
Related in: MedlinePlus