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Rosiglitazone, a Peroxisome Proliferator-Activated Receptor (PPAR)-γ Agonist, Attenuates Inflammation Via NF-κB Inhibition in Lipopolysaccharide-Induced Peritonitis

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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.

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ACKNOWLEDGMENTS

This work was funded by the Key Clinical Discipline Program of the Ministry of Health, China (Grant No. [2010]439), the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (Grant No. 2011BAI10B05), the Program of National Key Clinical Specialties, and Guangzhou Committee of Science and Technology, China (Grant No. 2010U1-E00831), and the program of Huadu district science and technology, Guangzhou, China (Grant No.13-HDWS2003).

Author Contributions

Prof Xiao YANG and Prof Xue-Qing YU conceived the study, participated in its design and coordination, and helped in drafting the manuscript. Dr. Yun-Fang ZHANG and Xun-Liang ZOU participated in study design, carried out the laboratory experiments, analyzed the data, interpreted the results, and wrote the manuscript. Jun WU carried out the laboratory experiments. All authors have approved the final version of the manuscript. We thank Ms. Xiu-Qing DONG and Dr Wen-Xing PENG for their technical advice and assistance.

Conflict of Interest

The authors declare that they have no competing interests.

Ethical approval

All experiments involving animals were approved by the Animal Care and Use Committee of the Sun Yat-sen University, Guangdong, China and carried out in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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    Authors and Affiliations

    1. Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou, 510080, China

      Yun-Fang Zhang, Xun-Liang Zou, Jun WU, Xue-Qing Yu & Xiao Yang

    2. Key Laboratory of Nephrology, Ministry of Health and Guangdong Province, Guangzhou, 510080, China

      Yun-Fang Zhang, Jun WU, Xue-Qing Yu & Xiao Yang

    3. Department of Nephrology, Huadu District People’s Hospital, Southern Medical University, 22 Baohua Road, Guangzhou, 510800, China

      Yun-Fang Zhang

    4. Department of Nephrology, The Second Affiliated Hospital Binjiang Branch, College of Medicine, Zhejiang University, 1511 Jiang Hong Road, Hangzhou, 310052, Zhejiang, China

      Xun-Liang Zou

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    1. Yun-Fang Zhang
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    Correspondence to Xiao Yang.

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    Yun-Fang Zhang and Xun-Liang Zou contributed equally to this work.

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    Zhang, YF., Zou, XL., WU, J. et al. Rosiglitazone, a Peroxisome Proliferator-Activated Receptor (PPAR)-γ Agonist, Attenuates Inflammation Via NF-κB Inhibition in Lipopolysaccharide-Induced Peritonitis. Inflammation 38, 2105–2115 (2015). https://doi.org/10.1007/s10753-015-0193-2

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