High insulin and leptin increase resistin and inflammatory cytokine production from human mononuclear cells

Panayoula C Tsiotra, Eleni Boutati, George Dimitriadis, Sotirios A Raptis, Panayoula C Tsiotra, Eleni Boutati, George Dimitriadis, Sotirios A Raptis

Abstract

Resistin and the proinflammatory cytokines, such as TNF- α , IL-6, and IL-1 β , produced by adipocytes, and macrophages, are considered to be important modulators of chronic inflammation contributing to the development of obesity and atherosclerosis. Human monocyte-enriched mononuclear cells, from ten healthy individuals, were exposed to high concentrations of insulin, leptin, and glucose (alone or in combination) for 24 hours in vitro. Resistin, TNF- α , IL-6, and IL-1 β production was examined and compared to that in untreated cells. High insulin and leptin concentrations significantly upregulated resistin and the cytokines. The subsequent addition of high glucose significantly upregulated resistin and TNF- α mRNA and protein secretion, while it did not have any effect on IL-6 or IL-1 β production. By comparison, exposure to dexamethasone reduced TNF- α , IL-6, and IL-1 β production, while at this time point it increased resistin protein secretion. These data suggest that the expression of resistin, TNF- α , IL-6, and IL-1 β from human mononuclear cells, might be enhanced by the hyperinsulinemia and hyperleptinemia and possibly by the hyperglycemia in metabolic diseases as obesity, type 2 diabetes, and atherosclerosis. Therefore, the above increased production may contribute to detrimental effects of their increased adipocyte-derived circulating levels on systemic inflammation, insulin sensitivity, and endothelial function of these patients.

Figures

Figure 1
Figure 1
Secreted resistin protein levels (a) and relative resistin/β-actin mRNA levels (b) from human monocyte-enriched mononuclear cells after in vitro exposure for 24 h to high concentrations of insulin, leptin, glucose, and dexamethasone. *P < 0.03 versus control cells, §P = 0.049 versus control cells.
Figure 2
Figure 2
Secreted TNF-α protein levels (a) and relative TNF-α/β-actin mRNA levels (b) from the human monocyte-enriched mononuclear cells after in vitro exposure for 24 h to high concentrations of insulin, leptin, glucose, and dexamethasone. *P < 0.045 versus control cells.
Figure 3
Figure 3
Secreted IL-6 protein levels (a) and relative IL-6/PBGD mRNA levels (b) from the human monocyte-enriched mononuclear cells after exposure to high concentrations of insulin, leptin, glucose, and dexamethasone. *P < 0.05 versus control cells.
Figure 4
Figure 4
Secreted IL-1β protein levels (a) and relative IL-1β/PBGD mRNA levels (b) from the human monocyte-enriched mononuclear cells after exposure to high concentrations of insulin, leptin, glucose, and dexamethasone. *P < 0.05 versus control cells, #P = 0.061 versus control cells.

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