Expression of cyclooxygenase-2 in intestinal goblet cells of pre-diabetic NOD mice
Abstract
Cyclooxygenase, the rate-limiting enzyme in prostaglandin synthesis, is expressed in constitutive (COX-1) and inducible (COX-2) isoforms. The COX-2 has been proposed to be involved in development of autoimmune type 1 diabetes (T1D). We examined COX-2 expression in the gut-associated lymphoid tissue (GALT), and found COX-2 was strongly expressed in goblet cells of non-obese diabetic (NOD) mice at the apical villi at the age of 2.5 weeks, clearly before the onset of insulitis, while the expression in the control BALB/c mice was weak or absent at all ages (P < 0.001). Lipopolysaccharide (LPS) given intraperitoneally slightly increased COX-2 expression in the goblet cells and epithelium of both NOD and BALB/c mice. High-resolution confocal microscopy showed that the surroundings of the goblet cells contained no COX-2, implying that the enzyme is synthesized by the goblet cells. The COX-2 is secreted from goblet cells into the intestinal lumen along with mucins. The COX-2 concentration in the goblet cell of BALB/c and especially of NOD mice was markedly higher than that in the intraepithelial lymphocytes or lamina propria macrophages. High mucin COX-2 from goblet cells may increase luminal prostaglandin synthesis, alter epithelial p...Continue Reading
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