Interleukin-1 Beta Regulates the Expression of a Leukocyte Type of 12-lipoxygenase in Rat Islets and RIN m5F Cells

Endocrinology. 1995 Dec;136(12):5736-44. doi: 10.1210/endo.136.12.7588331.

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 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 up-regulate 12-LO expression and activity in rat beta-cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • Animals
  • Arachidonate 12-Lipoxygenase / biosynthesis*
  • Arachidonate 12-Lipoxygenase / genetics
  • Base Sequence
  • Cells, Cultured
  • Humans
  • Hydroxyeicosatetraenoic Acids / biosynthesis
  • Immunohistochemistry
  • Interleukin-1 / pharmacology*
  • Islets of Langerhans / enzymology*
  • Male
  • Molecular Sequence Data
  • Nitric Oxide Synthase / biosynthesis
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Hydroxyeicosatetraenoic Acids
  • Interleukin-1
  • RNA, Messenger
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • Arachidonate 12-Lipoxygenase
  • Nitric Oxide Synthase