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Involvement of the Negative Feedback of IL-33 Signaling in the Anti-Inflammatory Effect of Electro-acupuncture on Allergic Contact Dermatitis via Targeting MicroRNA-155 in Mast Cells

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Abstract

In this study, we aimed to investigate the effect of electro-acupuncture (EA) at the Zusanli acupoint (ST36) on interleukin (IL)-33-mediated mast cell activation. Firstly, 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) in rats was developed with or without EA treatment. Then, rat peritoneal mast cells (RPMCs) were obtained and cultured in the presence of IL-33. EA treatment relieved ear swelling and reduced mast cell infiltration in the local inflammation area with DNFB challenge, accompanying the decrement of IL-33 production. RPMCs isolated from ACD rats with EA treatment showed significant downregulation of IL-6, TNF-α, IL-13, and MCP-1 production following IL-33 stimulation. However, there was no obvious difference in surface ST2 receptor expression among different groups. In addition, EA selectively altered IL-33 signaling, suppressing p38 phosphorylation as well as NF-κB- and AP-1-mediated transcription but not Akt phosphorylation. Importantly, EA lowered microRNA (miR)-155 expression in the RPMCs, which presented a positive correlation with IL-33-induced IL-6 production. Furthermore, overexpression of miR-155 in the RPMCs was established following miR-155 mimic transfection. RPMCs with the overexpressed miR-155 displayed an obvious increment of inflammatory cytokine and abrogated the inhibitive effect of EA on NF-κB- and AP-1-regulated transcription in response to IL-33 compared with those without transfected-miR-155. These findings demonstrate EA treatment inhibits NF-κB and AP-1 activation as well as promotes the negative feedback regulation of IL-33 signaling via targeting miR-155 in mast cells, which contribute to the anti-inflammatory effect of EA on DNFB-induced ACD in rats.

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Acknowledgments

This work was supported by the grants from the Specialized Fund of Hubei Provincial Department of Education in Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion (No. HBPCIC-2016-020) and Natural Science Foundation of Hubei Province of China (No. 2015CFA096).

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Authors and Affiliations

Authors

Contributions

Zhigang Wang, Tao Yi, and Zebin Chen designed the study; Zhigang Wang and Tao Yi performed the experiment and wrote the manuscript; Man Long contributed to the rat model; Fengmin Ding analyzed the data; and Lichen Ouyang and Zebin Chen helped to revise the manuscript.

Corresponding author

Correspondence to Zebin Chen.

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All experiments were performed according to the standard of the Animal Care and Use Committee of Hubei University of Chinese Medicine concerning the Care and Use of Laboratory Animals (No. SYXK2012-0067).

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The authors declare that they have no conflicts of interest.

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Wang, Z., Yi, T., Long, M. et al. Involvement of the Negative Feedback of IL-33 Signaling in the Anti-Inflammatory Effect of Electro-acupuncture on Allergic Contact Dermatitis via Targeting MicroRNA-155 in Mast Cells. Inflammation 41, 859–869 (2018). https://doi.org/10.1007/s10753-018-0740-8

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