Inhibitory effect of 3,4-dichloro-propionaniline on cytokine production by macrophages is associated with LPS-mediated signal transduction.
Our previous studies demonstrated that both in vivo and in vitro 3,4-dichloro-propionanilide (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-alpha 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 Ca2+ levels demonstrates that LPS-induced Ca2+ release is abrogated in propanil-treated macrophages. However, the binding of LPS to macrophages is not affected. Measurement of inositol 1,4,5-triphosphate (IP3) demonstrates that propanil significantly increases the level and the duration of IP3 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.
Xie
Y C
YC
Department of Microbiology and Immunology, School of Medicine, Robert C. Byrd Health Sciences Center of West Virginia University, Morgantown 26506-9177, USA.
Schafer
R
R
Barnett
J B
JB
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011411:Propanil / Q000633:toxicity*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D000093242:Interleukin-6 Inhibitors
D002118:Calcium; D016207:Cytokines; D015544:Inositol 1,4,5-Trisphosphate; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011411:Propanil; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors