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Recently, a human \u03b2-cell line, EndoC-\u03b2H1, has been derived from human fetal pancreatic buds. The purpose of this study was to determine whether human EndoC-\u03b2H1 cells respond to cytokines in a fashion comparable to human islets. Unlike most rodent-derived insulinoma cell lines that respond to cytokines in a manner consistent with rodent islets, EndoC-\u03b2H1 cells fail to respond to a combination of cytokines (IL-1, IFN-\u03b3, and TNF) in a manner consistent with human islets. Nitric oxide, produced following inducible nitric oxide synthase (iNOS) expression, is a major mediator of cytokine-induced human islet cell damage. We show that EndoC-\u03b2H1 cells fail to express iNOS or produce nitric oxide in response to this combination of cytokines. Inhibitors of iNOS prevent cytokine-induced loss of human islet cell viability; however, they do not prevent cytokine-induced EndoC-\u03b2H1 cell death. Stressed human islets or human islets expressing heat shock protein 70 (HSP70) are resistant to cytokines, and, much like stressed human islets, EndoC-\u03b2H1 cells express HSP70 under basal conditions. Elevated basal expression of HSP70 in EndoC-\u03b2H1 cells is consistent with the lack of iNOS expression in response to cytokine treatment. While expressing HSP70, EndoC-\u03b2H1 cells fail to respond to endoplasmic reticulum stress activators, such as thapsigargin. These findings indicate that EndoC-\u03b2H1 cells do not faithfully recapitulate the response of human islets to cytokines. Therefore, caution should be exercised when making conclusions regarding the actions of cytokines on human islets when using this human-derived insulinoma cell line.<\/jats:p>","DOI":"10.1152\/ajpregu.00544.2014","type":"journal-article","created":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T03:41:18Z","timestamp":1434598878000},"page":"R525-R534","source":"Crossref","is-referenced-by-count":49,"title":["Distinct differences in the responses of the human pancreatic \u03b2-cell line EndoC-\u03b2H1 and human islets to proinflammatory cytokines"],"prefix":"10.1152","volume":"309","author":[{"given":"Bryndon J.","family":"Oleson","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"McGraw","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna A.","family":"Broniowska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mani","family":"Annamalai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin R.","family":"Bushkofsky","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin, Madison, Wisconsin; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn B.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Wisconsin, Madison, Wisconsin; and"},{"name":"William S. 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