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Inhibitory effect of 3,4‐dichloropropionaniline on cytokine production by macrophages is associated with LPS‐mediated signal transduction
Author(s) -
Xie Y. C.,
Schafer R.,
Barnett J. B.
Publication year - 1997
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.61.6.745
Subject(s) - cytokine , lipopolysaccharide , biology , tumor necrosis factor alpha , propanil , stimulation , macrophage , signal transduction , in vivo , microbiology and biotechnology , in vitro , immunology , medicine , endocrinology , biochemistry , pesticide , agronomy
Abstract Our previous studies demonstrated that both in vivo and in vitro 3,4‐dichloropropionanilide (propanil) exposure inhibited interleukin‐6 (IL‐6) and tumor necrosis factor (TNF) production by adherent thioglycollate‐elicited peritoneal cells (macrophages) after lipopolysaccharide (LPS) stimulation. In this study, we report that IL‐6 and TNF‐α message is reduced by propanil in a concentration‐dependent pattern, yet the stability of cytokine mRNA is not affected. In addition, exposure of macrophages to propanil after a relatively short period of LPS stimulation significantly reduced the production of IL‐6 and TNF. Determination of the intracellular Ca 2+ levels demonstrates that LPS‐induced Ca 2+ release is abrogated in propaniltreated macrophages. However, the binding of LPS to macrophages is not affected. Measurement of inositol 1,4,5‐triphosphate (IP 3 ) demonstrates that propanil significantly increases the level and the duration of IP 3 in macrophages. These results suggest that the inhibitory effect of propanil on macrophage cytokine production is associated with the early stages of LPS‐mediated signal transduction in macrophages. J. Leukoc. Biol . 61: 745–752; 1997.