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Cytokine regulatory effects on α‐1 proteinase inhibitor expression in NOD mouse islet endothelial cells
Author(s) -
Papaccio Gianpaolo,
Pedullà Marcella,
Ammendola Eduardo,
Todaro Matilde
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10114
Subject(s) - nod , nod mice , genetically modified mouse , islet , cytokine , downregulation and upregulation , biology , transgene , microbiology and biotechnology , endocrinology , immunology , diabetes mellitus , biochemistry , gene
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 α‐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‐1β 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‐1β 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. J. Cell. Biochem. 85: 123–130, 2002. © 2002 Wiley‐Liss, Inc.