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Direct and indirect modulation of LPS-induced cytokine production by insulin in human macrophages

Title data

Klauder, Julia ; Henkel, Janin ; Vahrenbrink, Madita ; Wohlenberg, Anne-Sophie ; Camargo, Rodolfo Gonzalez ; Püschel, Gerhard Paul:
Direct and indirect modulation of LPS-induced cytokine production by insulin in human macrophages.
In: Cytokine. Vol. 136 (December 2020) . - Art.Nr. 155241.
ISSN 1043-4666
DOI: https://doi.org/10.1016/j.cyto.2020.155241

Abstract in another language

Overweight and obesity are accompanied by insulin resistance, impaired intestinal barrier function resulting in increased lipopolysaccharide (LPS) levels, and a low-grade chronic inflammation that results in macrophage activation. Macrophages produce a range of interleukins as well as prostaglandin E2 (PGE2). To cope with insulin resistance, hyperinsulinemia develops. The purpose of the study was to elucidate how LPS, insulin and PGE2 might interact to modulate the inflammatory response in macrophages. Human macrophages were either derived by differentiation from U937 cells or isolated from blood mononuclear cells. The macrophages were stimulated with LPS, insulin and PGE2. Insulin significantly enhanced the LPS-dependent expression of interleukin-1β and interleukin-8 on both the mRNA and protein levels. Additionally, insulin increased the LPS-dependent induction of enzymes involved in the PGE2-synthesis and the production of PGE2 by macrophages. PGE2 in turn further enhanced the LPS-dependent expression of cytokines via its Gs-coupled receptors EP2 and EP4, the latter of which appeared to be more relevant. The combination of all three stimuli resulted in an even higher induction than the combination of LPS plus insulin or LPS plus PGE2. Thus, the compensatory hyperinsulinemia might directly and indirectly enhance the LPS-dependent cytokine production in obese individuals.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: Cytokines & prostaglandins; Inflammation; Insulin; Macrophage; Metabolic syndrome & type II diabetes
Institutions of the University: Faculties > Faculty of Life Sciences: Food, Nutrition and Health
Result of work at the UBT: No
DDC Subjects: 500 Science
500 Science > 570 Life sciences, biology
Date Deposited: 26 Apr 2021 12:32
Last Modified: 26 Apr 2021 12:58
URI: https://eref.uni-bayreuth.de/id/eprint/64441