Induction of caspase‐11 by inflammatory stimuli in rat astrocytes: lipopolysaccharide induction through p38 mitogen‐activated protein kinase pathway

FEBS Letters

Kim, Sun Yeou³  Hur, Jinyoung³  Kim, Hocheol³  Suk, Kyoungho³  Cha, Sang-hoon¹  Lee, Myung-Shik² 

[1] Division of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chunchon, South Korea;Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea;Graduate School of East-West Medical Science and Research Institute for Basic Sciences, Kyunghee University, Seoul, South Korea

关键词: Caspase-11;    Astrocyte;    Inflammation;    Lipopolysaccharide;    Mitogen-activated protein kinase;    LPS;    lipopolysaccharide;    EAE;    experimental allergic encephalomyelitis;    MAPK;    mitogen-activated protein kinase;    ERK;    extracellular signal-regulated kinase;    JNK/SAPK;    c-Jun N-terminal kinase/stress-activated protein kinase;    CNS;    central nervous system;    iNOS;    inducible nitric oxide synthase;   

DOI  :  10.1016/S0014-5793(01)02975-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Caspase-11 plays a crucial role in both inflammation and apoptosis. Caspase-11 not only activates caspase-1, that is required for the maturation of proinflammatory cytokines such as interleukin (IL)-1 and IL-18, but also activates caspase-3, leading to cellular apoptosis under pathological conditions. Here, we cloned the rat homolog of caspase-11, and investigated its inducibility by inflammatory stimuli and signal transduction pathways involved. Deduced amino acid sequence of rat caspase-11 showed 88.7% similarity to mouse caspase-11, and in vitro translation of rat caspase-11 cDNA yielded approximately a 43 kDa polypeptide, which was in agreement with predicted protein size generated from full-length rat caspase-11 cDNA. The expression of caspase-11 was strongly induced at both mRNA and protein levels by inflammatory stimuli such as lipopolysaccharide (LPS), interferon-γ, and tumor necrosis factor-α in C6 rat glial cells as well as primary astrocytes. LPS induced activation of both p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) in C6 cells. However, SB203580 (specific inhibitor of p38 kinase), but not PD98059 (specific inhibitor of ERK kinase), inhibited LPS induction of caspase-11, indicating that induction of caspase-11 by LPS in astrocytes was mediated through the p38 MAPK pathway. Inflammatory induction of caspase-11 in astrocytes may play an important role in both inflammatory responses involving these cells and auto-regulatory apoptosis of activated astrocytes in inflammatory sites.

【 授权许可】

Unknown