Toll-like receptor 4 on islet β cells senses expression changes in high-mobility group box 1 and contributes to the initiation of type 1 diabetes
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作者:
Min Li
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机构:Zhongshan Hospital,Department of General Surgery
Min Li
Lujun Song
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机构:Zhongshan Hospital,Department of General Surgery
Lujun Song
Xiaodong Gao
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机构:Zhongshan Hospital,Department of General Surgery
Xiaodong Gao
Wenju Chang
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机构:Zhongshan Hospital,Department of General Surgery
Wenju Chang
Xinyu Qin
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机构:Zhongshan Hospital,Department of General Surgery
Xinyu Qin
机构:
[1] Zhongshan Hospital,Department of General Surgery
[2] Shanghai Medical School,undefined
[3] Fudan University,undefined
[4] Shanghai 200032,undefined
[5] China.,undefined
来源:
Experimental & Molecular Medicine
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2012年
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44卷
关键词:
diabetes mellitus, type 1;
HMGB1 protein;
islets of Langerhans;
mice, inbred NOD;
toll-like receptor 4;
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暂无
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摘要:
Type 1 diabetes mellitus is caused by the autoimmune destruction of β cells within the islets. In recent years, innate immunity has been proposed to play a key role in this process. High-mobility group box 1 (HMGB1), an inflammatory trigger in a number of autoimmune diseases, activates proinflammatory responses following its release from necrotic cells. Our aim was to determine the significance of HMGB1 in the natural history of diabetes in non-obese diabetic (NOD) mice. We observed that the rate of HMGB1 expression in the cytoplasm of islets was much greater in diabetic mice compared with non-diabetic mice. The majority of cells positively stained for toll-like receptor 4 (TLR4) were β cells; few α cells were stained for TLR4. Thus, we examined the effects of anti-TLR4 antibodies on HMGB1 cell surface binding, which confirmed that HMGB1 interacts with TLR4 in isolated islets. Expression changes in HMGB1 and TLR4 were detected throughout the course of diabetes. Our findings indicate that TLR4 is the main receptor on β cells and that HMGB1 may signal via TLR4 to selectively damage β cells rather than α cells during the development of type 1 diabetes mellitus.
机构:
Univ Calif Los Angeles, Dept Pediat, Div Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Dept Pediat, Div Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
Mazarati, Andrey
Maroso, Mattia
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机构:
Mario Negri Inst Pharmacol Res, Dept Neurosci, Milan, ItalyUniv Calif Los Angeles, Dept Pediat, Div Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
Maroso, Mattia
Iori, Valentina
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机构:
Mario Negri Inst Pharmacol Res, Dept Neurosci, Milan, ItalyUniv Calif Los Angeles, Dept Pediat, Div Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
Iori, Valentina
Vezzani, Annamaria
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Mario Negri Inst Pharmacol Res, Dept Neurosci, Milan, ItalyUniv Calif Los Angeles, Dept Pediat, Div Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
Vezzani, Annamaria
Carli, Mirjana
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机构:
Mario Negri Inst Pharmacol Res, Dept Neurosci, Milan, ItalyUniv Calif Los Angeles, Dept Pediat, Div Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA
机构:
Chinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R ChinaChinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R China
Zhu, Xiao-Mei
Yao, Yong-Ming
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Chinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R ChinaChinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R China
Yao, Yong-Ming
Liang, Hua-Ping
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机构:
Third Mil Med Univ, Daping Hosp, State Key Lab Trauma Burns & Combined Injury, Res Inst Surg,Dept 1, Chongqing 400042, Peoples R ChinaChinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R China
Liang, Hua-Ping
Xu, Chang-Tao
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Chinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R ChinaChinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R China
Xu, Chang-Tao
Dong, Ning
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机构:
Chinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R ChinaChinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R China
Dong, Ning
Yu, Yan
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机构:
Chinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R ChinaChinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R China
Yu, Yan
Sheng, Zhi-Yong
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机构:
Chinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R ChinaChinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Dept Microbiol & Immunol, Beijing 100048, Peoples R China