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Inflammation Research

Published in:

01-06-2014 | Original Research Paper

M3 mAChR-mediated IL-8 expression through PKC/NF-κB signaling pathways

Authors: Zu-Peng Xu, Yun Song, Kai Yang, Wei Zhou, Li-Na Hou, Liang Zhu, Hong-Zhuan Chen, Yong-Yao Cui

Published in: Inflammation Research | Issue 6/2014

Abstract

Objective

M3 muscarinic acetylcholine receptor (mAChR) plays an important role in the regulation of cytokine production in inflammatory diseases. In this study, we explored the precise role of M3 mAChR under stimulation with agonist in IL-8 expression and of the signaling pathway involved in this process.

Materials and methods

Recombinant U2OS cells stably expressing M3 mAChR as a model system were stimulated by carbachol to evaluate the role of M3 mAChR in the expression of IL-8.

Results

Activation of M3 mAChR with carbachol increased both IL-8 mRNA and protein expression in a concentration-dependent manner. Elevated IL-8 expression was completely antagonized by atropine, 4-DAMP and tiotropium. M3 mAChR-mediated IL-8 expression was almost completely inhibited by the NF-κB inhibitor BAY11-7082 and, to a lesser extent, by U0126, SB203580, and SP600125, which are inhibitors for ERK1/2, p38, and JNK, respectively. Furthermore, M3 mAChR-mediated NF-κB activation and IL-8 expression were simultaneously attenuated by the PKC inhibitor calphostin C, whereas PMA, a PKC activator, mimicked the effects of carbachol, inducing IL-8 expression.

Conclusions

Our findings offer insights into the specific and critical role of M3 mAChR in regulating inflammatory response and indicate M3 mAChR/PKC/NF-κB signaling axis driven by endogenous acetylcholine as a potential therapeutic targets for inflammatory diseases.

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Title: M3 mAChR-mediated IL-8 expression through PKC/NF-κB signaling pathways
Authors: Zu-Peng Xu
Yun Song
Kai Yang
Wei Zhou
Li-Na Hou
Liang Zhu
Hong-Zhuan Chen
Yong-Yao Cui
Publication date: 01-06-2014
Publisher: Springer Basel
Published in: Inflammation Research / Issue 6/2014
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-014-0718-4

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M3 mAChR-mediated IL-8 expression through PKC/NF-κB signaling pathways

Abstract

Objective

Materials and methods

Results

Conclusions

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Conclusions

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