title: Rosiglitazone, a Peroxisome Proliferator-Activated Receptor (PPAR)-γ Agonist, Attenuates Inflammation Via NF-κB Inhibition in Lipopolysaccharide-Induced Peritonitis.
abstract: We assessed the anti-inflammatory effect of peroxisome proliferator-activated receptor (PPAR)-γ agonist, rosiglitazone, in a lipopolysaccharide (LPS)-induced peritonitis rat model. LPS was intraperitoneally injected into rats to establish peritonitis model. Male Sprague-Dawley (SD) rats were assigned to normal saline (the solvent of LPS), LPS, rosiglitazone plus LPS, and rosiglitazone alone. A simple peritoneal equilibrium test was performed with 20 ml 4.25 % peritoneal dialysis fluid. We measured the leukocyte count in dialysate and ultrafiltration volume. Peritoneal membrane histochemical staining was performed, and peritoneal thickness was assessed. CD40 and intercellular adhesion molecule-1 messenger RNA (ICAM-1 mRNA) levels in rat visceral peritoneum were detected by reverse transcription (RT)-PCR. IL-6 in rat peritoneal dialysis effluent was measured using enzyme-linked immunosorbent assay. The phosphorylation of NF-κB-p65 and IκBα was analyzed by Western blot. LPS administration resulted in increased peritoneal thickness and decreased ultrafiltration volume. Rosiglitazone pretreatment significantly decreased peritoneal thickness. In addition to CD40 and ICAM-1 mRNA expression, the IL-6, p-p65, and p-IκBα protein expressions were enhanced in LPS-administered animals. Rosiglitazone pretreatment significantly decreased ICAM-1 mRNA upregulation, secretion of IL-6 protein, and phosphorylation of NF-κB-p65 and IκBα without decreasing CD40 mRNA expression. Rosiglitazone has a protective effect in peritonitis, simultaneously decreasing NF-κB phosphorylation, suggesting that NF-κB signaling pathway mediated peritoneal inflammation induced by LPS. PPAR-γ might be considered a potential therapeutic target against peritonitis.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China. zhang_yunf@163.com.|Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, 510080, China. zhang_yunf@163.com.|Department of Nephrology, Huadu District People's Hospital, Southern Medical University, 22 Baohua Road, Guangzhou, 510800, China. zhang_yunf@163.com.
authors.forename: Yun-Fang
authors.initials: YF
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China. zxlkid@126.com.|Department of Nephrology, The Second Affiliated Hospital Binjiang Branch, College of Medicine, Zhejiang University, 1511 Jiang Hong Road, Hangzhou, 310052, Zhejiang, China. zxlkid@126.com.
authors.forename: Xun-Liang
authors.initials: XL
authors.lastname: Zou
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China. doctorwujun@163.com.|Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, 510080, China. doctorwujun@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China. yuxq@mail.sysu.edu.cn.|Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, 510080, China. yuxq@mail.sysu.edu.cn.
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Yu
authors.affiliation: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China. yangxsysu@126.com.|Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, 510080, China. yangxsysu@126.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D010537:Peritoneum / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D019013:CD40 Antigens; D020672:I-kappa B Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D047495:PPAR gamma; D012333:RNA, Messenger; C498145:Rela protein, rat; D045162:Thiazolidinediones; D051996:Transcription Factor RelA; C440499:lipopolysaccharide, Escherichia coli O111 B4; D000077154:Rosiglitazone; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha
keywords: NF-κB; inflammation; peritonitis; peroxisome proliferator-activated receptor (PPAR)-γ; rosiglitazone