INTERLEUKIN-1-BETA REGULATES THE EXPRESSION OF A LEUKOCYTE TYPE OF 12-LIPOXYGENASE IN RAT ISLETS AND RIN M5F CELLS

被引：38

作者：

BLEICH, D ^{[1
]}

CHEN, SY ^{[1
]}

GU, JL ^{[1
]}

THOMAS, L ^{[1
]}

SCOTT, S ^{[1
]}

GONZALES, N ^{[1
]}

NATARAJAN, R ^{[1
]}

NADLER, JL ^{[1
]}

机构：

[1] CITY HOPE NATL MED CTR, DEPT DIABET ENDOCRINOL & METAB, DUARTE, CA 91010 USA

来源：

ENDOCRINOLOGY | 1995年 / 136卷 / 12期

关键词：

D O I：

10.1210/en.136.12.5736

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The leukocyte type of 12-lipoxygenase (12-LO) may play a role in inflammatory reactions in many cell types through the conversion of arachidonic acid to proinflammatory eicosanoids that include 12-hydroperoxyeicosatetraenoic acid and 12-hydroeicosatetraenoic acid. Previous studies demonstrating the presence of a functional 12-LO pathway in rat and human pancreatic beta-cells plus the recent cloning of a rat leukocyte type of 12-LO allowed us to evaluate whether inflammatory cytokines such as interleukin-1 beta (IL-1 beta) can regulate the beta-cell 12-LO enzyme pathway, thus providing a potential link between the cytotoxic effects of cytokines on pancreatic beta-cells and the proinflammatory effects of 12-LO products. We demonstrate that IL-1 beta induces 12-LO protein and messenger RNA (mRNA) expression in RIN m5F cells and 12-LO mRNA expression in rat islets. RIN m5F cells treated for 16 h with IL-1 beta (25, 50, and 100 ng/liter) showed a maximal 2-fold increase in the expression of a leukocyte form of 12-LO demonstrated by Western blots. A concomitant increase in 12-LO mRNA expression was seen at this time point using a highly sensitive competitive polymerase chain reaction assay. The increase in mRNA and protein expression was preceded by increased 12-LO pathway activity measured by a RIA for 12-S-HETE. Separate experiments using purified Sprague-Dawley rat islets also showed increased expression of 12-LO mRNA and enzyme activity in response to IL-1 beta. These results demonstrate that IL-1 beta can upregulate 12-LO expression and activity in rat beta-cells.

引用

页码：5736 / 5744

页数：9

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