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H. pylori related proinflammatory cytokines contribute to the induction of miR-146a in human gastric epithelial cells

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Abstract

MicroRNAs have been implicated as a central regulator of the immune system. We have previously reported that Helicobacter pylori (H. pylori) was able to increase the expression of miR-146a, and miR-146a may negatively regulate H. pylori-induced inflammation, but the exact mechanism of how H. pylori contribute the induction of miR-146a is not clear. Here, we attempted to assess the role of H. pylori related proinflammatory cytokines including interleukin (IL)-8, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β, and cytotoxin-associated gene A (CagA) virulence factor on the induction of miR-146a. We found that IL-8, TNF-α, and IL-1β could contribute to the induction of miR-146a in gastric epithelial cell HGC-27 in NF-κB-dependent manner, while the induction of miR-146a upon H. pylori stimulation was independent of above proinflammatory cytokines. Furthermore, overexpression of miR-146a reduced H. pylori—induced IL-8, TNF-α, and IL-1β. However, CagA had no effect on the miR-146a induction. Taken together, our study suggest that proinflammatory cytokines IL-8, TNF-α, and IL-1β could contribute to the induction of miR-146a during H. pylori infection, while CagA is not necessarily required for miR-146a induction. miR-146a may function as novel negative regulators to modulate the inflammation.

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Acknowledgments

The authors would like to thank Dr. Masato Suzuki and Prof. Chihiro Sasakawa (Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo) for providing ∆cagA NCTC11637 H. pylori strain and CagA expression plasmid. This work was supported by the Scientific Innovation Research Foundation of Third Military Medical University (No. 2009XQN20), and Chinese National Natural Science Foundation project (No. 30770113), and grant from the Project of State Key Laboratory of Trauma, Burns, and Combined Injury (No. SKF201012).

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Authors and Affiliations

  1. Department of Clinical Microbiology and Immunology, College of Medical Laboratory Science, Third Military Medical University, Chongqing, 400038, People’s Republic of China

    Na Li, Bin Xiao, En-Dong Zhu, Bo-sheng Li, Zhen Liu, Bin Tang, Quan-Ming Zou & Xu-Hu Mao

  2. State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, 400042, China

    Xiang Xu & Hua-Ping Liang

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  1. Na Li
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  2. Xiang Xu
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  3. Bin Xiao
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  4. En-Dong Zhu
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  5. Bo-sheng Li
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  6. Zhen Liu
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  7. Bin Tang
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  8. Quan-Ming Zou
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  9. Hua-Ping Liang
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  10. Xu-Hu Mao
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Corresponding authors

Correspondence to Bin Xiao, Hua-Ping Liang or Xu-Hu Mao.

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Na Li and Xiang Xu contributed equally to this work.

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Li, N., Xu, X., Xiao, B. et al. H. pylori related proinflammatory cytokines contribute to the induction of miR-146a in human gastric epithelial cells. Mol Biol Rep 39, 4655–4661 (2012). https://doi.org/10.1007/s11033-011-1257-5

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  • DOI: https://doi.org/10.1007/s11033-011-1257-5

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