Cox-2 Expressed with Insulin in Pancreatic Beta-Cells, and in the Infiltrated Leukocytes in Inflamed Islets of Diabetic Mice

Abstract

In the event of the onset of type 1 diabetes (T1D) the circulating autoantibodies against the beta-cell of the pancreas are attacked by macrophages and autoreactive lymphocytes under the influence of different cytokines. Eventually, beta-cells are destroyed through apoptosis, or natural killer cells, or a scavenger process. Cyclooxygenase (COX)-2 is constitutively expressed in beta-cells, the possible role in insulin secretion and insulitis has been suggested. However, COX-2 with lymphocytes and other infiltrated leukocytes on diabetogenesis remains largely elusive. We injected diabetic lymphocytes of non-obese diabetic (NOD) mice to NOD/SCID mice for adoptive transfer. The diabetogenesis of adoptive transferred NOD/SCID mice was tested with supplements of COX-2 inhibitor or the substrate, arachidonic acid, in the diets under placebo control. The tissues of intestine and pancreas of BALB/c, NOD and NOD/SCID mice were immunohistochemically analyzed. COX-2 and insulin were revealed in the vesicles of beta-cells in intact islets of BALB/c mice. The lymphocyte tracking of the transferred lymphocytes and COX-2 expression in beta-cells and emerged leukocytes showed that celecoxib, or the substrate did not change the pattern of lymphocyte accumulation in the pancreas compared to placebo, even though the development of severe diabetes was slightly different. COX-2 was only expressed in macrophages, rather than infiltrated lymphocytes. Morphology showed that the emerged lymphocytes migrated from outside islets indicating that the disructive impact of COX-2 on beta cells is probably limited. The enhanced expression of COX-2 and insulin in random beta-cells is likely associated with the genesis of diabetes, a possible mechanism to increase or extend insulin secretion in the late period of insulitis.