Tim-4 protects mice against lipopolysaccharide-induced endotoxic shock by suppressing the NF-κB signaling pathway.
Endotoxic shock is the primary cause of morbidity and mortality in hospital patients, creating an urgent need to explore the mechanisms involved in sepsis. Our previous studies showed that T-cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4) attenuated the inflammatory response through regulating the functions of macrophages. However, the mechanism by which Tim-4 does this has not been fully elucidated. In this study, we found that Tim-4 expression was increased in lipopolysaccharide (LPS)-induced endotoxic shock. Interestingly, the survival rate of mice in the Tim-4 overexpression group was higher than that of the control group after LPS administration. To investigate the function of Tim-4 in LPS-induced inflammation, we further demonstrated that Tim-4 attenuated LPS-induced endotoxic shock by inhibiting cytokine production by macrophages. Blocking expression of Tim-4 and nuclear factor-kappa B (NF-κB) signal inhibition showed that Tim-4 inhibited cytokine production via NF-κB signaling pathway. This study indicates that Tim-4 may exert its immune modulation by regulating inflammatory factor secretion and might act as a novel potential target for inflammatory diseases, especially endotoxic shock.
Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, Jinan, Shandong, China.|Cell and Molecular Biology Laboratory, Zhoushan Hospital, Zhoushan, Zhejiang, China.
Liyun
L
Xu
Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, Jinan, Shandong, China.|Department of Central Laboratory, Zibo Central Hospital, Zibo, Shandong, China.
Peiqing
P
Zhao
Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
Yong
Y
Xu
College of Science and Engineering, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Lishuang
L
Gao
Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
Hongxing
H
Wang
Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
Xiaoxia
X
Jia
Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
Hongxin
H
Ma
Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
Xiaoxong
X
Liang
Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
Chunxong
C
Ma
Department of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong Provincial Key Laboratory of Infection & Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
Lifen
L
Gao
D000818:Animals; D002460:Cell Line; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism* / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; C500399:TIM-4 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse