Limits...
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.

Show MeSH

Related in: MedlinePlus

Effects of RGDS on LPS-induced increases in total protein levels in BAL fluid. Where indicated, mice were administered i.p. RGDS (1, 2.5 or 5 mg/kg) or RGES (5 mg/kg) once 1 h before LPS and sacrificed 4 h post-LPS (A). Mice were also administered these peptides (5 mg/kg, i.p.) once 1 h before or 2 h after LPS and were sacrificed 24 h post-LPS (B). Values represent means ± SEM of 5 mice per group. *Significantly different from saline treated controls, p < 0.05; +significantly different from animals treated with LPS only, p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2666640&req=5

Figure 3: Effects of RGDS on LPS-induced increases in total protein levels in BAL fluid. Where indicated, mice were administered i.p. RGDS (1, 2.5 or 5 mg/kg) or RGES (5 mg/kg) once 1 h before LPS and sacrificed 4 h post-LPS (A). Mice were also administered these peptides (5 mg/kg, i.p.) once 1 h before or 2 h after LPS and were sacrificed 24 h post-LPS (B). Values represent means ± SEM of 5 mice per group. *Significantly different from saline treated controls, p < 0.05; +significantly different from animals treated with LPS only, p < 0.05.

Mentions: LPS treatment significantly increased protein content in BAL fluid at 4 and 24 h post-LPS, by 1.5- and 2.6-fold, respectively, compared with saline treated controls (Figures 3A and 3B). RGDS (2.5 or 5 mg/kg, 1 h before LPS) significantly decreased protein levels at 4 h post-LPS by 70 and 73%, respectively (p < 0.05) (Figure 3A). At 24 h post-LPS, RGDS treatment 1 h before or 2 h after LPS, similarly and significantly inhibited this LPS-induced BAL protein increase by 62, and 64% vs. LPS, respectively (p < 0.05) (Figure 3B). LPS+RGES or saline+RGDS had no effect on protein accumulation compared with LPS- or saline-treated mice, respectively.


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)

Effects of RGDS on LPS-induced increases in total protein levels in BAL fluid. Where indicated, mice were administered i.p. RGDS (1, 2.5 or 5 mg/kg) or RGES (5 mg/kg) once 1 h before LPS and sacrificed 4 h post-LPS (A). Mice were also administered these peptides (5 mg/kg, i.p.) once 1 h before or 2 h after LPS and were sacrificed 24 h post-LPS (B). Values represent means ± SEM of 5 mice per group. *Significantly different from saline treated controls, p < 0.05; +significantly different from animals treated with LPS only, p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Effects of RGDS on LPS-induced increases in total protein levels in BAL fluid. Where indicated, mice were administered i.p. RGDS (1, 2.5 or 5 mg/kg) or RGES (5 mg/kg) once 1 h before LPS and sacrificed 4 h post-LPS (A). Mice were also administered these peptides (5 mg/kg, i.p.) once 1 h before or 2 h after LPS and were sacrificed 24 h post-LPS (B). Values represent means ± SEM of 5 mice per group. *Significantly different from saline treated controls, p < 0.05; +significantly different from animals treated with LPS only, p < 0.05.
Mentions: LPS treatment significantly increased protein content in BAL fluid at 4 and 24 h post-LPS, by 1.5- and 2.6-fold, respectively, compared with saline treated controls (Figures 3A and 3B). RGDS (2.5 or 5 mg/kg, 1 h before LPS) significantly decreased protein levels at 4 h post-LPS by 70 and 73%, respectively (p < 0.05) (Figure 3A). At 24 h post-LPS, RGDS treatment 1 h before or 2 h after LPS, similarly and significantly inhibited this LPS-induced BAL protein increase by 62, and 64% vs. LPS, respectively (p < 0.05) (Figure 3B). LPS+RGES or saline+RGDS had no effect on protein accumulation compared with LPS- or saline-treated mice, respectively.

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