Regular Article

Cell and Tissue Research

, Volume 310, Issue 2, pp 169-175

First online:

Cellular distribution and contribution of cyclooxygenase (COX)-2 to diabetogenesis in NOD mouse

  • Cheng LuoAffiliated withJuvenile Diabetes Research Foundation (FDRF) Center for Prevention of Type 1 Diabetes in Finland, University of Turku, Turku, Finland
  • , Markku KallajokiAffiliated withDepartment of Pathology, University of Turku, Turku, Finland
  • , Rene GrossAffiliated withUMR 5094 du Centre National de la Recherche Scientifique (CNRS), Université Montpellier I, Montpellier, France
  • , Mika MulariAffiliated withDepartment of Anatomy, University of Turku, Turku, Finland
  • , Tamara TerosAffiliated withJuvenile Diabetes Research Foundation (FDRF) Center for Prevention of Type 1 Diabetes in Finland, University of Turku, Turku, Finland
  • , Laura YlinenAffiliated withJuvenile Diabetes Research Foundation (FDRF) Center for Prevention of Type 1 Diabetes in Finland, University of Turku, Turku, Finland
  • , Marjaana MäkinenAffiliated withJuvenile Diabetes Research Foundation (FDRF) Center for Prevention of Type 1 Diabetes in Finland, University of Turku, Turku, Finland
  • , Jukka LaineAffiliated withDepartment of Pathology, University of Turku, Turku, Finland
  • , Olli SimellAffiliated withJuvenile Diabetes Research Foundation (FDRF) Center for Prevention of Type 1 Diabetes in Finland, University of Turku, Turku, Finland

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Abstract.

Unlike most other mammalian cells, β-cells of Langerhans constitutively express cyclooxygenase (COX)-2 rather than COX-1. COX-2 is also constitutively expressed in type 1 diabetes (T1D) patients' periphery blood monocytes and macrophage. To understand the role of COX-2 in the β-cell, we investigated COX-2 expression in β-cells and islet infiltrates of NOD and BALB/c mice using fluorescence immunohistochemistry and cytochemical confocal microscopy and Western blotting. Immunostaining showed that COX-2 is expressed in islet-infiltrating macrophages, and that the expression of insulin and COX-2 disappeared concomitantly from the β-cells when NOD mice progressed toward overt diabetes. Also cultured INS-1E cells coexpressed insulin and COX-2 but clearly in different subcellular compartments. Treatment with celecoxib increased insulin release from these cells in a dose-dependent manner in glucose concentrations ranging from 5 to 17 mM. Excessive COX-2 expression by the islet-infiltrating macrophages may contribute to the β-cell death during insulitis. The effects of celecoxib on INS-1E cells suggest that PGE2 and other downstream products of COX-2 may contribute to the regulation of insulin release from the β-cells.

COX-2 Macrophage Confocal microscopy INS-1 cells Non obese diabetic (NOD) mouse Mouse (BALB/c)