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Th2 cytokines have a partial, direct protective effect on the function and survival of isolated human islets exposed to combined proinflammatory and Th1 cytokines.

Title: Th2 cytokines have a partial, direct protective effect on the function and survival of isolated human islets exposed to combined proinflammatory and Th1 cytokines.
Authors: Marselli L.; Piro S.; Santangelo C.; Masini M.; Lupi R.; Realacci M.; del Guerra S.; Mosca F.; Boggi U.; Purrello F.; Navalesi R.; Marchetti P.; DOTTA, FRANCESCO
Contributors: Marselli, L.; Dotta, Francesco; Piro, S.; Santangelo, C.; Masini, M.; Lupi, R.; Realacci, M.; del Guerra, S.; Mosca, F.; Boggi, U.; Purrello, F.; Navalesi, R.; Marchetti, P.
Publication Year: 2001
Collection: Università degli Studi di Siena: USiena air
Description: Studies in rodents have suggested that Th2 and Th3 cytokines can be effective in reducing proinflammatory and Th1 cytokine-induced islet damage. Whether this is the case with human islets and might be due to a direct action of Th2 and Th3 cytokines is not known. In the present study, we evaluated whether Th2 (500 U/ml IL-4 plus 100 U/ml IL-10) or Th3 (5 ng/ml TGF-1beta) cytokines may prevent the derangements induced on isolated human islets by prolonged (12 or 72 h) exposure to combined proinflammatory (50 U/ml IL-1beta, 1000 U/ml TNF alpha) and Th1 (1000 U/ml interferon gamma) cytokines. Compared with control islets, cells preincubated for 12 or 72 h with proinflammatory and Th1 cytokines showed a significant decrease of glucose-stimulated insulin secretion and a significant increase of nitrites production. The addition of IL-4 plus IL-10 or TGF-1beta in the medium prevented these cytostatic effects in the 12-h incubation experiments, but not after the 72-h exposure period. IL-1beta, interferon gamma, and TNF alpha caused no major change in either islet cell survival or Bcl-2 and Bax mRNA expression after a 12-h incubation; however, a marked increase in the amount of dead cells, with a major decrease of Bcl-2 mRNA expression, was observed after 72 h. The presence of Th2, but not of Th3, cytokines significantly reduced beta-cell death, without any major effect on Bcl-2 and Bax mRNA expression. These results suggest that Th2 and (at lower extent) Th3 cytokines may have a partial, direct protective effect on isolated human islets exposed to the cytostatic and cytotoxic action of proinflammatory and Th1 cytokines.
Document Type: article in journal/newspaper
File Description: ELETTRONICO
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/11600573; info:eu-repo/semantics/altIdentifier/wos/WOS:000171755400069; volume:86; issue:10; firstpage:4974; lastpage:4978; numberofpages:5; journal:THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM; http://hdl.handle.net/11365/34742
DOI: 10.1210/jc.86.10.4974
Availability: http://hdl.handle.net/11365/34742; https://doi.org/10.1210/jc.86.10.4974
Rights: info:eu-repo/semantics/closedAccess
Accession Number: edsbas.47F0321E
Database: BASE