Neutralization of interleukin-1 beta attenuates silica-induced lung inflammation and fibrosis in C57BL/6 mice

被引：115

作者：

Guo, Jiali ^{[1
,2
]}

Gu, Nali ^{[1
,2
]}

Chen, Jie ^{[3
]}

Shi, Tingming ^{[4
]}

Zhou, Yun ^{[1
,2
]}

Rong, Yi ^{[1
,2
]}

Zhou, Ting ^{[1
,2
]}

Yang, Wenxiang ^{[4
]}

Cui, Xiuqing ^{[1
,2
]}

Chen, Weihong ^{[1
,2
]}

机构：

[1] Huazhong Univ Sci & Technol, Sch Publ Hlth, Tongji Med Coll, Dept Occupat & Environm Hlth, Wuhan 430030, Hubei, Peoples R China

[2] Huazhong Univ Sci & Technol, Sch Publ Hlth, Tongji Med Coll, Minist Educ,Key Lab Environm & Hlth, Wuhan 430030, Hubei, Peoples R China

[3] China Med Univ, Sch Publ Hlth, Div Pneumoconiosis, Shenyang 110001, Liaoning, Peoples R China

[4] Hubei Ctr Dis Control & Prevent, Inst Hlth Surveillance Anal & Protect, Wuhan 430070, Hubei, Peoples R China

来源：

ARCHIVES OF TOXICOLOGY | 2013年 / 87卷 / 11期

基金：

中国国家自然科学基金;

关键词：

Silica; IL-1; beta; Lung inflammation; Lung fibrosis; NALP3; INFLAMMASOME; PULMONARY-FIBROSIS; INNATE; MECHANISMS; OVEREXPRESSION; PATHOGENESIS; ANTAGONIST; ACTIVATION; EXPRESSION; MEDIATORS;

D O I：

10.1007/s00204-013-1063-z

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

The inflammation and fibrosis induced by silica dust are considered to be substantial responses in silicosis progression. Interleukin-1 beta (IL-1 beta) plays an important role in silica-induced lung inflammation, but the mechanisms that underlie the influence of IL-1 beta on the progression of silicosis remain unclear. In this study, the role of IL-1 beta in silica-induced inflammation and fibrosis was evaluated by administering a suspension of 2.5-mg silica dust, either with or without 40 mu g anti-mouse IL-1 beta monoclonal antibody (mAb), to the lungs of male C57BL/6 mice. Silica + anti-IL-1 beta mAb-treated mice showed the depletion of IL-1 beta as well as the attenuation of inflammation, as evaluated in the bronchoalveolar lavage fluid (BALF) and histological sections from 1 to 84 days after silica exposure. Further study of the BALF indicated that inhibition of IL-1 beta could reduce the contents of tumor necrosis factor-alpha and monocyte chemoattractant protein-1. The real-time PCR and pathology results showed that the neutralization of IL-1 beta attenuated silica-induced fibrosis by inhibiting the gene expression of transforming growth factor-beta 1, collagen I and fibronectin. The examination of Th1-cytokine and Th2-cytokine suggested that depletion of IL-1 beta decelerated the Th1/Th2 balance toward a Th2-dominant response. In conclusion, the present study suggests that the neutralization of IL-1 beta attenuates silica-induced inflammation and fibrosis by inhibiting other inflammatory and fibrogenic mediators and modulating the Th1/Th2 balance.

引用

页码：1963 / 1973

页数：11

共 39 条

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