Cytokine regulatory effects on alpha-1 proteinase inhibitor expression in NOD mouse islet endothelial cells.
Human microvascular islet endothelial cells (IEC) exhibit specific morphological and functional characteristics that differ from endothelia derived from other organs. One of these characteristics is the expression of alpha-1 proteinase inhibitor (Api). In this study, we observed its expression in nonobese diabetic (NOD) mouse IEC, in relation to the occurrence of type 1 diabetes and in response to cytokines, namely IL-1 beta and IL-10. In addition, IL-10-deficient NOD mice as well as IL-10 transgenic NODs were studied. Results have demonstrated that Api expression is: (i) highly specific for IEC in NOD mouse islets, as for humans; (ii) linked to the occurrence of early type 1 diabetes, and iii) strongly modulated by Th1 and Th2 cytokines. In fact, Api mRNA found in pre-diabetic NOD animals is significantly reduced when they become hyperglycemic and disappears by 25 weeks of age, when mice are diabetic. Moreover, Api mRNAs are never seen in nondiabetic controls. Furthermore, in cultured NOD IEC, Api expression is downregulated by the addition of IL-1 beta and is upregulated by IL-10; it is always absent in IL-10-deficient NOD mice and overexpressed in IL-10 transgenic NODs, thus further supporting that this cytokine upregulates Api expression.
Papaccio
Gianpaolo
G
Department of Experimental Medicine, Laboratory of Histology, School of Medicine, 2nd University of Naples, 5 via L. Armanni, 80138 Naples, Italy. gianpaolo.papaccio@unina2.it
Pedullà
Marcella
M
Ammendola
Eduardo
E
Todaro
Matilde
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007375:Interleukin-1 / Q000494:pharmacology*; D016753:Interleukin-10 / Q000172:deficiency / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D012107:Research Design / Q000592:standards; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000295:instrumentation; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis* / Q000235:genetics
D001786:Blood Glucose; D007375:Interleukin-1; D000515:alpha 1-Antitrypsin; D016753:Interleukin-10