In:
Diabetes, American Diabetes Association, Vol. 55, No. 12 ( 2006-12-01), p. 3439-3445
Abstract:
Type 1 diabetes is caused by adaptive immune responses, but innate immunity is important because monocytes infiltrate islets. Activated monocytes express cyclooxygenase (COX)-2, promoting prostaglandin-E2 (PGE2) secretion, whereas COX-1 expression is constitutive. We aimed to define monocyte COX expression in type 1 diabetes basally and after lipopolysaccharide (LPS) stimulation. Isolated CD14+ monocytes were analyzed for COX mRNA and protein expression from identical twins (discordant for type 1 diabetes) and control subjects. Basal monocyte COX mRNA, protein expression, and PGE2 secretion were normal in type 1 diabetic subjects. After LPS, twins and control subjects showed a COX mRNA isoform switch with decreased COX-1 mRNA (P & lt; 0.01), increased COX-2 mRNA (P & lt; 0.01), and increased COX-2 protein expression (P & lt; 0.01). Compared with control subjects, both diabetic and nondiabetic twins showed greater LPS-induced downregulation of monocyte COX-1 mRNA (P = 0.02), reduced upregulation of COX-2 mRNA and protein (P & lt; 0.03), and greater inhibition by the COX-2 inhibitor di-isopropylfluorophosphate (DFP) of monocyte PGE2 (P & lt; 0.007). We demonstrate an alteration in monocyte COX mRNA expression as well as monocyte COX-2 and PGE2 production after LPS in type 1 diabetic patients and their nondiabetic twins. Because COX-2 response to LPS is proinflammatory, an inherited reduced response would predispose to chronic inflammatory diseases such as type 1 diabetes.
Type of Medium:
Online Resource
ISSN:
0012-1797
,
1939-327X
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2006
detail.hit.zdb_id:
1501252-9
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