Differential suppression of endotoxin-inducible inflammatory cytokines by nuclear factor kappa B (NFkappaB) inhibitor in rat microglia.
The molecular mechanism by which the deleterious cytokines interleukin 1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) are induced in endotoxin-stimulated microglia was investigated from the viewpoint of signal transduction. Neither cytokine is produced in nonstimulated rat microglia, but both are remarkably induced by stimulation with endotoxin lipopolysaccharide (LPS). LPS-inducible IL-1beta was significantly suppressed by pretreatment with the nuclear factor kappa B (NFkappaB) inhibitor ammonium pyrrolidine dithiocarbamate (APDC), but TNFalpha was not. APDC was actually confirmed to suppress the degradation of IkappaBalpha and IkappaBbeta in microglia, indicating a role for the inhibitor of NFkappaB activation. Taken together, these results suggest that the induction of IL-1beta and TNFalpha in endotoxin-stimulated microglia is differentially regulated at the level of NFkappaB activation.
Department of Bioinformatics, Faculty of Engineering, Soka University, Hachioji, Tokyo 192-8577, Japan. nakajima@t.soka.ac.jp
Kazuyuki
K
Nakajima
Yuichi
Y
Matsushita
Yoko
Y
Tohyama
Shinichi
S
Kohsaka
Tadashi
T
Kurihara
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D013859:Thiocarbamates / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid