Nicotine induces TIPE2 upregulation and Stat3 phosphorylation contributes to cholinergic anti-inflammatory effect

Sui,Hua Xiu; Ke,Shi Zhong; Xu,Dan Dan; Lu,Nan Nan; Wang,Yi Nan; Zhang,Yue Hua; Gao,Feng Guang

doi:10.3892/ijo.2017.4080

Nicotine induces TIPE2 upregulation and Stat3 phosphorylation contributes to cholinergic anti-inflammatory effect

Authors:
- Hua Xiu Sui
- Shi Zhong Ke
- Dan Dan Xu
- Nan Nan Lu
- Yi Nan Wang
- Yue Hua Zhang
- Feng Guang Gao
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Affiliations: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Published online on: July 27, 2017 https://doi.org/10.3892/ijo.2017.4080
Pages: 987-995

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Abstract

Cholinergic anti-inflammatory pathway has therapeutic effect on inflammation-associated diseases. However, the exact mechanism of nicotine-mediated anti-inflammatory effect is still unclear. TIPE2, a new member of tumor necrosis factor-α-induced protein-8 family, is a negative regulator of immune homeostasis. However, the roles of TIPE2 in cholinergic anti-inflammatory effect are still uncertain. Here, we demonstrated that nicotine exerts its anti-inflammatory effect by TIPE2 upregulation and phosphorylated stat3 mediated the inhibition of NF-κB activation, which was supported by the following evidence: firstly, both nicotine and TIPE2 inhibit pro-inflammatory cytokine release via NF-κB inactivation. Secondly, nicotine upregulates TIPE2 expression via α7 nicotinic acetylcholine receptor. Moreover, the enhancement of stat3 phosphorylation and decrease of LPS-induced p65 translocation were achieved by nicotine treatment. Importantly, nicotine treatment augments the interaction of phosphorylated stat3 and p65, indicating that the inhibitory effect of nicotine on NF-κB activation was mediated with protein-protein interactions. Hence, this study revealed that TIPE2 upregulation and stat3 phosphorylation contribute to nicotine-mediated anti-inflammation effect, indicating that TIPE2 and stat3 might be potential molecules for dealing with inflammation-associated diseases.

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