Induction of caspase-11 by inflammatory stimuli in rat astrocytes: lipopolysaccharide induction through p38 mitogen-activated protein kinase pathway.
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-gamma, and tumor necrosis factor-alpha 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.
Hur
J
J
Graduate School of East-West Medical Science and Research Institute for Basic Sciences, Kyunghee University, Seoul, South Korea.
Kim
S Y
SY
Kim
H
H
Cha
S
S
Lee
M S
MS
Suk
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics; D053471:Caspases, Initiator; D002460:Cell Line; D003001:Cloning, Molecular; D004789:Enzyme Activation; D004790:Enzyme Induction; D004791:Enzyme Inhibitors; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008969:Molecular Sequence Data; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D008070:Lipopolysaccharides; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C101136:Casp4 protein, mouse; C491071:Casp4 protein, rat; D020169:Caspases; D053471:Caspases, Initiator; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one