Activation of peroxisome proliferator-activated receptor-gamma potentiates pro-inflammatory cytokine production, and adrenal and somatotropic changes of weaned pigs after Escherichia coli lipopolysaccharide challenge.
Our previous study demonstrated mRNA and protein expression of peroxisome proliferator-activated receptor-g (PPAR-g) in the immune system of weaned pigs. In this report, to test the hypothesis that activation of PPAR-g in immune system modulates inflammatory response, and adrenal and somatotropic responses associated with immune challenge, we administered intraperitoneally PPAR-g agonist and/or antagonist in weaned pigs subjected to Escherichia coli lipopolysaccharide (LPS) challenge. Unexpectedly, we found that a single injection of the PPAR-g 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-a (TNF-a) and interleukin-6 (IL-6), mRNA abundance of TNF-a in thymus, spleen, mesenteric lymph node and peripheral white blood cells, mRNA abundance of IL-6 in thymus, protein levels of TNF-a 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-g antagonist bisphenol A diglycidyl ether (given 30 mg/kg body weight) 30 min prior to treatment with rosiglitazone antagonized the effect of the PPAR-g agonist, indicating a PPAR-g-dependent effect. Our data indicate that ligand-induced activation of PPAR-g 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-g 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.
Liu
Yulan
Y
Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, China. yulanflower@126.com
Shi
Junxia
J
Lu
Jing
J
Meng
Guoquan
G
Zhu
Huiling
H
Hou
Yongqing
Y
Yin
Yulong
Y
Zhao
Shengjun
S
Ding
Binying
B
D000818:Animals; D001559:Benzhydryl Compounds; D016207:Cytokines / Q000096:biosynthesis*; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000494:pharmacology; D015232:Dinoprostone / Q000819:agonists / Q000097:blood; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000494:pharmacology; D004926:Escherichia coli / Q000276:immunology; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D006854:Hydrocortisone / Q000819:agonists / Q000097:blood; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000276:immunology*; D000077154:Rosiglitazone; D013552:Swine / Q000276:immunology / Q000382:microbiology; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014886:Weaning; D000093242:Interleukin-6 Inhibitors; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D016207:Cytokines; D004121:Dimethyl Sulfoxide; D015232:Dinoprostone; D004852:Epoxy Compounds; D016166:Free Radical Scavengers; D006854:Hydrocortisone; D007334:Insulin-Like Growth Factor I; D015850:Interleukin-6; D008070:Lipopolysaccharides; D047495:PPAR gamma; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C019273:bisphenol A diglycidyl ether; D000098826:Bisphenol A Compounds