Regulation of the mRNA expression for tumor necrosis factor-alpha in rat liver macrophages.
Kupffer cells are known to produce tumor necrosis factor-alpha upon stimulation with endotoxin or viruses. This tumor necrosis factor-alpha synthesis is suppressed by prostaglandin E2 or dexamethasone. Using Northern blotting and reverse transcriptase-polymerase chain reaction, it is demonstrated that endotoxin-induced tumor necrosis factor-alpha synthesis is blocked by prostaglandin E2 or dibutyryl 3':5'-cyclic adenosine monophosphate on the transcriptional level. Tumor necrosis factor-alpha itself suppressed endotoxin-evoked tumor necrosis factor-alpha mRNA expression when given in a narrow time interval with lipopolysaccharide. Interleukin-10 of human or mouse origin also inhibited the synthesis of tumor necrosis factor-alpha mRNA and protein when given more than 2 h prior to the endotoxin challenge. The suppressive effect of prostaglandin E2 lasted for more than 36 h while IL-10 blocked tumor necrosis factor-alpha production for barely 24 h. Dexamethasone reduced the endotoxin-induced tumor necrosis factor-alpha mRNA formation by approximately 50% only, although it led to nearly complete inhibition of the synthesis of the mature protein. Taken together with reverse transcriptase-polymerase chain reaction data revealing significant amounts of tumor necrosis factor-alpha mRNA in resting Kupffer cells, an additional posttranscriptional regulation of tumor necrosis factor-alpha synthesis has to be assumed. Tumor necrosis factor-alpha mRNA was not induced by interferon-gamma, interleukin-1 beta or interleukin-6 (the latter two cytokines are also synthesized by Kupffer cells), but a 24-h prestimulation of liver macrophages with interferon-gamma or phorbol ester had a modest priming effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Grewe
M
M
Biochemisches Institut, Universität Freiburg, Germany.
Gausling
R
R
Gyufko
K
K
Hoffmann
R
R
Decker
K
K
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005938:Glucocorticoids / Q000502:physiology; D007728:Kupffer Cells / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D016207:Cytokines; D005938:Glucocorticoids; D011453:Prostaglandins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha