REGULATION OF THE MESSENGER-RNA EXPRESSION FOR TUMOR-NECROSIS-FACTOR-ALPHA IN RAT-LIVER MACROPHAGES

被引:53
作者
GREWE, M [1 ]
GAUSLING, R [1 ]
GYUFKO, K [1 ]
HOFFMANN, R [1 ]
DECKER, K [1 ]
机构
[1] UNIV FREIBURG,INST BIOCHEM,D-79104 FREIBURG,GERMANY
关键词
3'-5'-CYCLIC ADENOSINE MONOPHOSPHATE; CYTOKINE; DEXAMETHASONE; ENDOTOXIN; INTERFERON-GAMMA; INTERLEUKIN-10; KUPFFER CELLS; LIPOPOLYSACCHARIDE; PHORBOL ESTER; PROSTAGLANDIN E(2);
D O I
10.1016/S0168-8278(05)80154-0
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Kupffer cells are known to produce tumor necrosis factor-a upon stimulation with endotoxin or viruses. This tumor necrosis factor-alpha synthesis is suppressed by prostaglandin E(2) or dexamethasone. Using Northern blotting and reverse transcriptase-polymerase chain reaction, it is demonstrated that endotoxin-induced tumor necrosis factor-a synthesis is blocked by prostaglandin E(2) 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 E(2) lasted for more than 36 h while IL-10 blocked tumor necrosis factor-a 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. Other substances known to stimulate rat Kupffer cells, such as phorbol ester or calcium ionophore, did not lead to the induction of tumor necrosis factor-alpha or to an alteration of the lipopolysaccharide-induced tumor necrosis factor-alpha mRNA synthesis at 90 min or 24 h after stimulation. Comparison with findings on tumor necrosis factor-alpha mRNA synthesis in some macrophage-related cell lines, monocytes and freshly differentiated macrophages suggests that organ-specific differentiation of resident macrophages leads to;variations in the regulation of tumor necrosis factor-alpha mRNA production. (C) Journal of Hepatology.
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页码:811 / 818
页数:8
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