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The Vagus Nerve and Nicotinic Receptors Involve Inhibition of HMGB1 Release and Early Pro-inflammatory Cytokines Function in Collagen-Induced Arthritis

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Abstract

Objectives

The cholinergic anti-inflammatory pathway, a vagus nerve-dependent mechanism, inhibits cytokine releases in models of acute inflammatory disease. We investigated the efficacy and elucidated the possible mechanism of the cholinergic anti-inflammatory pathway on collagen-induced arthritis (CIA) in mice.

Methods

Fifty-six male DBA/1 mice were divided into four groups: control mice (sham vagotomy + phosphate-buffered saline; shamVGX+PBS), model mice (shamVGX+PBS+CIA), vagotomy mice (VGX+PBS+CIA), and nicotine (Nic) mice (shamVGX+Nic+CIA). We subjected mice to left-side cervical vagotomy 4 days before induction of arthritis. Mice in the nicotine group were injected with nicotine (250 μg/kg per day) 4 days before arthritis induction. Arthritis score was measured and histopathologic assessment of joint sections carried out. The concentration of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in serum were evaluated by ELISA. Expression of high-mobility group box chromosomal protein 1(HMGB1) was evaluated by immunohistochemical staining of joints.

Results

Vagotomy exaggerated, whereas nicotine attenuated, clinical arthritis. Histopathologic findings confirmed that nicotine reduced infiltration of inflammatory cell and bone destruction. Expression of TNF-α and IL-6 decreased in nicotine-pretreated mice compared with model and vagotomy mice; IL-10 levels were not significantly different between the model group and nicotine group. Nicotine reduced the expression and translocation of HMGB1 in the inflamed joints of CIA mice.

Conclusions

The cholinergic anti-inflammatory pathway has an anti-inflammatory role in the pathophysiology of rheumatoid arthritis (RA) via inhibiting HMGB1 release and early pro-inflammatory cytokines function. Study of this pathway could be used for RA therapy.

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Abbreviations

CIA:

Collagen-induced arthritis

ShamVGX:

Sham vagotomy

PBS:

Phosphate-buffered saline

Nic:

Nicotine

TNF:

Tumor necrosis factor

IL:

Interleukin

HMGB:

High-mobility group box chromosomal protein

RA:

Rheumatoid arthritis

TGF:

Transforming growth factor

CNS:

Central nervous system

MIP:

Macrophage inflammatory protein

LPS:

Lipopolysaccharide

ELISA:

Enzyme-linked immunosorbent assay

EDTA:

Ethylene diamine tetra-acetic acid

H&E:

Hematoxylin and erosin

PGE:

Prostaglandin E

MMPs:

Metallproteinases

NO:

Nitric oxide

TNFR:

TNF receptor

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Acknowledgements

This work was supported by grant from the National Natural Science Foundation of China [30671947].

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Authors and Affiliations

  1. Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, People’s Republic of China

    Tong Li, Xiaoxia Zuo, Yaou Zhou & Yanping Wang

  2. Department of Geratology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China

    Hanping Zhuang

  3. Laboratory of Shock, Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410008, People’s Republic of China

    Lingli Zhang, Huali Zhang & Xianzhong Xiao

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  1. Tong Li
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  2. Xiaoxia Zuo
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  3. Yaou Zhou
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Correspondence to Xiaoxia Zuo or Xianzhong Xiao.

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Li, T., Zuo, X., Zhou, Y. et al. The Vagus Nerve and Nicotinic Receptors Involve Inhibition of HMGB1 Release and Early Pro-inflammatory Cytokines Function in Collagen-Induced Arthritis. J Clin Immunol 30, 213–220 (2010). https://doi.org/10.1007/s10875-009-9346-0

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  • DOI: https://doi.org/10.1007/s10875-009-9346-0

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