Journal
INNATE IMMUNITY
Volume 15, Issue 3, Pages 169-178Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1753425908102014
Keywords
Peroxisome proliferator-activated receptor gamma; lipopolysaccharide; weaned pigs; rosiglitazone; bisphenol A diglycidyl ether; pro-inflammatory cytokines
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Funding
- National Natural Science Foundation of China [30500362]
- National Basic Research Program of China [2004CB117504]
- Key Project of Chinese Ministry of Education [209082]
- Youth Scholars Foundation of Wuhan, China [20055003059- 46]
- Natural Science Foundation of Hubei Province [2005ABA091]
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Our previous study demonstrated mRNA and protein expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in the immune system of weaned pigs. In this report, to test the hypothesis that activation of PPAR-gamma in immune system modulates inflammatory response, and adrenal and somatotropic responses associated with immune challenge, we administered intraperitoneally PPAR-gamma agonist and/or antagonist in weaned pigs subjected to Escherichia coli lipopolysaccharide (LPS) challenge. Unexpectedly, we found that a single injection of the PPAR-gamma agonist rosiglitazone (given at 3 mg/kg body weight 30 min before LPS injection) failed to block pro-inflammatory cytokine production induced by LPS injection. Rather, plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), mRNA abundance of TNF-alpha in thymus, spleen, mesenteric lymph node and peripheral white blood cells, mRNA abundance of IL-6 in thymus, protein levels of TNF-alpha in spleen and mesenteric lymph node, and protein levels of IL-6 in spleen and mesenteric lymph node, were elevated beyond the levels in control pigs injected with LPS. Furthermore, rosiglitazone potentiated the increase of plasma cortisol and prostaglandin E-2 concentrations, and the decrease of plasma insulin-like growth factor-1 concentration induced by LPS injection. Co-administration of the PPAR-gamma antagonist bisphenol A diglycidyl ether (given 30 mg/kg body weight) 30 min prior to treatment with rosiglitazone antagonized the effect of the PPAR-gamma agonist, indicating a PPAR-g-dependent effect. Our data indicate that ligand-induced activation of PPAR-gamma does not ameliorate but enhances pro-inflammatory cytokine production, and further potentiates the adrenal and somatotropic changes in weaned pigs subjected to E. coli LPS challenge, which suggests that PPAR-gamma activation may not be useful, but potentially harmful, in the treatment of immune challenge in livestock. Our results raise doubts about the prevalently accepted anti-inflammatory role for PPAR-g activation.
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