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

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Hur J,Kim SY,Kim H,Cha S,Lee MS,Suk K

doi

10.1016/s0014-5793(01)02975-1

keywords:

subject

Has Abstract

pub_date

2001-10-26 00:00:00

pages

157-62

issue

2

eissn

0014-5793

issn

1873-3468

pii

S0014579301029751

journal_volume

507

pub_type

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