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PPARγ agonist pioglitazone inhibits microglia inflammation by blocking p38 mitogen-activated protein kinase signaling pathways

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Abstract

Objective

The aim of this paper was to investigate the inhibitory effect of peroxisome proliferator-activated receptor-gamma (PPARγ) agonist pioglitazone on microglia inflammation induced by lipopolysaccharide (LPS).

Materials and methods

Highly aggressively proliferating immortalized cells were used from a rat microglial cell line. Expression of PPARγ, inducible NO synthase (iNOS), the p42/44 extracellular signal-regulated kinase (ERK) MAPKs, c-Jun NH2-terminal kinases (JNKs) and p38 MAPK were determined by Western blot analysis. The protein levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay. The production of nitric oxide (NO) was determined by a Nitric Oxide Assay Kit. The subcellular localization of PPARγ was studied by immunofluorescence microscopy analysis and nuclear-cytosolic fractionation technology, respectively. The transcriptional activity of PPARγ was detected by PPRE-Luciferase transcription assay.

Results

Pioglitazone effectively inhibited NO, iNOS, TNF-α, IL-6, IL-1β production in LPS-stimulated microglial cells. Additionally, pioglitazone suppressed PPARγ loss; enhanced transcriptional activity of PPARγ; and inhibited nucleus-export of PPARγ in microglia induced by LPS. And p38 MAPK inhibitor SB203580 had the similarity effects with pioglitazone. Signal transduction studies indicated that pioglitazone blocked the phosphorylation of p38 MAPK challenged by LPS.

Conclusion

The results show that pioglitazone can inhibit LPS-stimulated microglia inflammation by blocking p38 MAPK signaling pathway.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No.30770488 and No.30870320); Natural Science Foundation of Jiangsu province (No.BK2006547); A special Research Grant(XK 2007 23) for the key laboratory from the Department of Health, Jiangsu Province.

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Authors and Affiliations

  1. Laboratory Center, Affiliated Hospital of Nantong University, Nantong, 226001, China

    Huoyan Ji, Huimin Wang & Shen Aiguo

  2. Department of Microbiology and Immunology, Medical College, Nantong University, Nantong, 226001, China

    Fupeng Zhang, Xiaohong Li & Shen Aiguo

  3. The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, China

    Lu Xiang

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  1. Huoyan Ji
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  2. Huimin Wang
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  3. Fupeng Zhang
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  4. Xiaohong Li
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  5. Lu Xiang
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  6. Shen Aiguo
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Correspondence to Lu Xiang or Shen Aiguo.

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Responsible Editor: L. Li.

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Ji, H., Wang, H., Zhang, F. et al. PPARγ agonist pioglitazone inhibits microglia inflammation by blocking p38 mitogen-activated protein kinase signaling pathways. Inflamm. Res. 59, 921–929 (2010). https://doi.org/10.1007/s00011-010-0203-7

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  • DOI: https://doi.org/10.1007/s00011-010-0203-7

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