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Cytochalasin D inhibits lipopolysaccharide‐induced tumor necrosis factor production in macrophages
Author(s) -
Shinji Hitomi,
Akagawa Kiyoko S.,
Yoshida Takeshi
Publication year - 1993
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.54.4.336
Subject(s) - microfilament , lipopolysaccharide , cytochalasin d , tumor necrosis factor alpha , cytochalasin b , biology , cytochalasin , microbiology and biotechnology , stimulation , actin , macrophage , prostaglandin e2 , cytoskeleton , immunology , endocrinology , biochemistry , in vitro , cell
We reported previously that a reorganization of microfilaments can be observed when macrophages are stimulated with lipopolysaccharide (LPS). This reorganization is not detected with current methods in macrophages of an LPS‐nonresponsive C3H/HeJ mouse. These results suggest that the observed microfilament response might be involved in a macrophage‐activating process induced by LPS. To investigate this, we studied the effect of cytochalasin D (CD), which inhibits reorganization of microfilaments, on LPS‐induced tumor necrosis factor (TNF) production. A concentration of CD incapable of affecting filamentous actin by itself was used in these experiments. When this concentration of CD was added after LPS stimulation, microfilament reorganization and TNF production were inhibited. The suppressive effect of CD on TNF production was confirmed by the observation that TNF‐α mRNA expression was also inhibited by CD. This inhibitory effect of CD was not specific to TNF, because the production of interleukin‐1 and prostaglandin E 2 were also inhibited. These effects of CD were observed only when CD was added within the first 20 min after LPS stimulation. These results suggest that the CD‐ sensitive microfilament response is essential in the signaling pathway for the production of certain monokines in LPS‐stimulated macrophages.