Dataset Information

The novel role of platelet-activating factor in protecting mice against lipopolysaccharide-induced endotoxic shock.

ABSTRACT:

Background

Platelet-activating factor (PAF) has been long believed to be associated with many pathophysiological processes during septic shock. Here we present novel activities for PAF in protecting mice against LPS-mediated endotoxic shock.

Principal findings

In vivo PAF treatment immediately after LPS challenge markedly improved the survival rate against mortality from endotoxic shock. Administration of PAF prominently attenuated LPS-induced organ injury, including profound hypotension, excessive polymorphonuclear neutrophil infiltration, and severe multiple organ failure. In addition, PAF treatment protects against LPS-induced lymphocytes apoptosis. These protective effects of PAF was correlated with significantly decreases in the production of the inflammatory mediators such as TNF-alpha, IL-1beta, IL-12, and IFN-gamma, while increasing production of the anti-inflammatory cytokine IL-10 in vivo and in vitro.

Conclusions

Taken together, these results suggest that PAF may protect mice against endotoxic shock via a complex mechanism involving modulation of inflammatory and anti-inflammatory mediators.

SUBMITTER: Jeong YI

PROVIDER: S-EPMC2714981 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The novel role of platelet-activating factor in protecting mice against lipopolysaccharide-induced endotoxic shock.

Jeong Young-Il YI Jung In Duk ID Lee Chang-Min CM Chang Jeong Hyun JH Chun Sung Hak SH Noh Kyung Tae KT Jeong Soo Kyung SK Shin Yong Kyoo YK Lee Won Suk WS Kang Mi Sun MS Lee Sang-Yull SY Lee Jae-Dong JD Park Yeong-Min YM

PloS one 20090804 8

<h4>Background</h4>Platelet-activating factor (PAF) has been long believed to be associated with many pathophysiological processes during septic shock. Here we present novel activities for PAF in protecting mice against LPS-mediated endotoxic shock.<h4>Principal findings</h4>In vivo PAF treatment immediately after LPS challenge markedly improved the survival rate against mortality from endotoxic shock. Administration of PAF prominently attenuated LPS-induced organ injury, including profound hypo ...[more]

PMID: 19652714

Similar Datasets

Project description:Fisetin is a naturally occurring flavonoid that possesses several pharmacological benefits including anti-inflammatory activity. However, its precise anti-inflammatory mechanism is not clear. In the present study, we found that fisetin significantly inhibited the expression of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Additionally, fisetin attenuated LPS-induced mortality and abnormalities in zebrafish larvae and normalized the heart rate. Fisetin decreased the recruitment of macrophages and neutrophils to the LPS-microinjected inflammatory site in zebrafish larvae, concomitant with a significant downregulation of proinflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase-2a (COX-2a), IL-6, and TNF-α. Fisetin inhibited the nuclear localization of nuclear factor-kappa B (NF-κB), which reduced the expression of pro-inflammatory genes. Further, fisetin inactivated glycogen synthase kinase 3β (GSK-3β) via phosphorylation at Ser9, and inhibited the degradation of β-catenin, which consequently promoted the localization of β-catenin into the nucleus. The pharmacological inhibition of β-catenin with FH535 reversed the fisetin-induced anti-inflammatory activity and restored NF-κB activity, which indicated that fisetin-mediated activation of β-catenin results in the inhibition of LPS-induced NF-κB activity. In LPS-microinjected zebrafish larvae, FH535 promoted the migration of macrophages to the yolk sac and decreased resident neutrophil counts in the posterior blood island and induced high expression of iNOS and COX-2a, which was accompanied by the inhibition of fisetin-induced anti-inflammatory activity. Altogether, the current study confirmed that the dietary flavonoid, fisetin, inhibited LPS-induced inflammation and endotoxic shock through crosstalk between GSK-3β/β-catenin and the NF-κB signaling pathways.

Dataset Information

The novel role of platelet-activating factor in protecting mice against lipopolysaccharide-induced endotoxic shock.

Background

Principal findings

Conclusions

Publications

The novel role of platelet-activating factor in protecting mice against lipopolysaccharide-induced endotoxic shock.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets