Cytokine gene expression in the islets of the diabetic Biobreeding/Worcester rat.
The Biobreeding Worcester rat provides one of the best models of autoimmune diabetes. Immunopathologic studies of acute diabetes show that the islets are infiltrated by T cells and macrophages. It has been hypothesized that the islets are damaged by the secretion of cytokines such as IL-1 and TNF-alpha and that their function may be altered by IL-6. In this study, we utilized in situ hybridization to determine the expression of the IL-1, TNF, and IL-6 genes within the pancreas of the acute diabetic Biobreeding Worcester rat. These studies showed that cells expressing IL-1, TNF, and IL-6 were present within the islets and in the exocrine pancreas surrounding islets, ducts, and vessels and in an interstitial location. Cells expressing TNF and IL-1 mRNA were present in about 20% of the islets, whereas cells expressing IL-6 were present in about 4% of the islets. Islets containing TNF- or IL-1-positive cells contained about three positive cells per islet whereas only about one IL-6-positive cell was present per islet. In 26% of the islets peri-insular TNF-positive cells were found. Peri-insular IL-1 positive cells were seen in 14% of the islets and 8% showed peri-insular IL-6 positive cells. In nondiabetic 30-day old DP or 90-day-old DR rats intra-islet cytokine gene expression was not seen. Our studies support the view that cytokines are important in beta cell destruction.
Jiang
Z
Z
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655.
Woda
B A
BA
D000818:Animals; D015152:Blotting, Northern; D016207:Cytokines / Q000235:genetics*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D015870:Gene Expression; D007249:Inflammation / Q000503:physiopathology; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007515:Islets of Langerhans / Q000473:pathology / Q000503:physiopathology*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011922:Rats, Mutant Strains; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha