Title: Rosiglitazone as a Regulator of Innate Immunity in a Cell Model of Hyperglycemia Author(sстатья
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Статья опубликована в журнале из перечня ВАК
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
Аннотация:Epidemiological studies have shown that severe inflammatory responses occur in patients with hyperglycemia. The molecular nature of these changes is currently under intense investigation. A central role of nuclear receptors PPAR has been shown in the regulation of metabolic changes associated with hyperglycemia; a selective agonist of nuclear receptor PPAR gamma rosiglitazone is used as a hypoglycemic drug. Rosiglitazone is known to have anti-inflammatory effects, but its properties as an anti-inflammatory drug in hyperglycemic conditions have not been studied. In this work, we used a human cell culture model of hyperglycemia: HeLa cells incubated at glucose concentration of 25 mM for 3 days. Control cells were incubated at glucose concentration of 5 mM. The cells were stimulated with lipopolysaccharide (LPS) that affects innate immunity through activation of Toll-like receptor 4, and mRNA expression levels of three isotypes of PPAR (alpha, beta/delta, gamma) and cyclooxygenase (COX-1 and COX-2) were estimated. We have shown that under hyperglycemic conditions expression levels of PPAR alpha and PPAR beta/delta are decreased almost twofold, expression level of COX-2 is also decreased, while expression levels of COX-1 and PPAR gamma remain unchanged as compared to those under normal glucose concentration. LPS administration in control cells led to a 1.5-2.5-fold stimulation of the expression of COX-2 and PPAR isotypes. In contrast, under hyperglycemia, LPS exhibited no effect on the expression of COX-2 and PPAR isotypes, which indicates potential mechanisms of hyperglycemia-related alterations in innate immunity. Rosiglitazone, an agonist of PPAR gamma, decreased expression level of PPAR beta/delta and abolished the effect of LPS under hyperglycemia. Rosiglitazone also reduced expression level of COX-1 and COX-2, which indicates that this agonist can be used as an anti-inflammatory agent under high glucose concentrations. These data broaden applicability of rosiglitazone as an anti-inflammatory agent in hyperglycemic conditions.