Expression of cyclooxygenase-2 in intestinal goblet cells of pre-diabetic NOD mice.
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 permeability, modulate intestinal immune responses and modify functional properties of the lymphocytes in the GALT, which all may be important for the initiation of the autoimmune phenomenon in the NOD mice.
Luo
C
C
The Juvenile Diabetes Research Foundation Center for Prevention of Type 1 Diabetes in Finland, University of Turku, Turku, Finland.
Laine
V J O
VJ
Ylinen
L
L
Teros
T
T
Mäkinen
M
M
Ristimäki
A
A
Simell
O
O
D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D020397:Goblet Cells / Q000201:enzymology* / Q000378:metabolism; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000166:cytology / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D007527:Isoenzymes; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases