Interleukin-1 β regulates the expression of a leukocyte type of 12-lipoxygenase in rat islets and rin m5f cells

David Bleich, Songyuan Chen, Jia Li Gu, Lisa Thomas, Stephen Scott, Noe Gonzales, Rama Natarajan, Jerry L. Nadler

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

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 β (IL-1 β) can regulate the β-cell 12-LO enzyme pathway, thus providing a potential link between the cytotoxic effects of cytokines on pancreatic β-cells and the proinflammatory effects of 12-LO products. We demonstrate that IL-1 β 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 β (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 β. These results demonstrate that IL-1 β can up-regulate 12-LO expression and activity in rat β-cells.

Original languageEnglish (US)
Pages (from-to)5736-5744
Number of pages9
JournalEndocrinology
Volume136
Issue number12
DOIs
StatePublished - Apr 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrinology

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    Bleich, D., Chen, S., Gu, J. L., Thomas, L., Scott, S., Gonzales, N., Natarajan, R., & Nadler, J. L. (1995). Interleukin-1 β regulates the expression of a leukocyte type of 12-lipoxygenase in rat islets and rin m5f cells. Endocrinology, 136(12), 5736-5744. https://doi.org/10.1210/endo.136.12.7588331