ICEECE2012 Poster Presentations Nuclear receptors and Signal transduction (17 abstracts)
1Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; 2Nippon Medical School, Tokyo, Japan.
Introduction: Postoperative sepsis exhibits high mortality. Prevention of postoperative infection and palliation of sepsis symptom are important issues in the patients care after surgical operation. Adipose tissue as an endocrine organ that secretes various cytokines. Circulating adiponectin, an anti-inflammatory cytokine, and inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α are derived partially from adipose tissues. Recent studies have suggested that adipose tissue may play an important role in systemic inflammatory response. Our previous report also demonstrated that preoperative circulating adiponectin levels may be a risk factor of postoperative infection. We examined here whether a PPARγ activator, pioglitazone (PGZ) which increases serum adiponectin level may suppress excessive inflammatory reaction accompanying with sepsis in the mouse sepsis model.
Method: Seven-week old mice were treated with PGZ (10 mg/kg, i.p.) for 7 days and sepsis was induced by cecal ligation and puncture (CLP). The survival rate was monitored, and inflammatory factors in peritoneal fluid (PF) and abdominal adipose tissue were analyzed by real-time PCR and ELISA 24 h after CLP. In addition, abdominal adipocyte was cultured in the presence or absence of CLP mice-derived PF with PGZ to determine direct effects of PF on inflammatory cytokine expressions in adipocytes.
Result and conclusion: Serum adiponectin levels before CLP were elevated after PGZ treatment and the survival rate after CLP was improved. CLP increased IL-6 and TNF-α mRNA expressions in abdominal adipose tissues, and also TNF-α and endotoxin levels in PF. PGZ pretreatment inhibited TNF-α expression without the suppression of endotoxin. PF collected from CLP mice stimulated IL-6 and TNF-α expression in cultured abdominal adipocytes. However, these cytokines levels were significantly lower when PF derived from PGZ-treated CLP mice was applied in adipocytes. These results suggest that pretreatment of PPARγ activator possibly improves the survival rate by down-regulating excessive inflammation in adipose tissues.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.