Mice deficient in hepatocyte-specific IL-1Ra show delayed resolution of concanavalin A-induced hepatitis

被引：16

作者：

Lamacchia, Celine ^{[1
,2
]}

Rodriguez, Emiliana ^{[1
,2
]}

Palmer, Gaby ^{[1
,2
]}

Vesin, Christian ^{[3
]}

Seemayer, Christian A. ^{[4
]}

Rubbia-Brandt, Laura ^{[2
,5
]}

Gabay, Cem ^{[1
,2
]}

机构：

[1] Univ Geneva, Sch Med, Div Rheumatol, Univ Hosp, CH-1211 Geneva, Switzerland

[2] Univ Geneva, Sch Med, Dept Pathol & Immunol, CH-1211 Geneva, Switzerland

[3] Univ Geneva, Sch Med, Dept Cellular Physiol & Metab, CH-1211 Geneva, Switzerland

[4] Novartis Pharma AG, Basel, Switzerland

[5] Univ Geneva, Sch Med, Div Clin Pathol, Univ Hosp, CH-1211 Geneva, Switzerland

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 2012年 / 42卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

Cytokine; IL-1; inhibitor; Inflammation; Liver; Necrosis; INTERLEUKIN-1 RECEPTOR ANTAGONIST; TUMOR-NECROSIS-FACTOR; ACUTE-PHASE PROTEIN; AUTOINFLAMMATORY DISEASE; TNF-ALPHA; LIVER; IL-1-BETA; GENE; INFLAMMATION; EXPRESSION;

D O I：

10.1002/eji.201142204

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Interleukin-1 receptor antagonist (IL-1Ra) is a specific IL-1 inhibitor that possesses anti-inflammatory activities. Several studies in human and mouse suggested a protective role for IL-1Ra in liver inflammation, and we previously demonstrated that hepatocytes produce high levels of IL-1Ra in response to inflammatory challenge in vitro and in vivo. In the present study, we investigated the production and the biological function of hepatocyte-derived IL-1Ra in concanavalin A (ConA)-induced hepatitis in mice. We show that the injured liver produces large amounts of IL-1Ra and that secreted and intracellular IL-1Ra isoforms are produced with different kinetics during the course of hepatitis. By using hepatocyte-specific IL-1Ra-deficient mice (IL-1Ra?H), we demonstrate that hepatocytes represent the major cellular source of local IL-1Ra. Most interestingly, hepatic necrosis and inflammation were increased in IL-1Ra?H as compared with wild-type mice during the late phase of the disease, leading to a delayed resolution of hepatitis in IL-1Ra?H mice. In conclusion, our results show that the local production of IL-1Ra by hepatocytes contributes to the resolution of hepatitis.

引用

页码：1294 / 1303

页数：10