TY  - JOUR
A1  - Henkel, Janin
A1  - Klauder, Julia
A1  - Statz, Meike
A1  - Wohlenberg, Anne-Sophie
A1  - Kuipers, Sonja
A1  - Vahrenbrink, Madita
A1  - Püschel, Gerhard Paul
T1  - Enhanced Palmitate-Induced Interleukin-8 Formation in Human Macrophages by Insulin or Prostaglandin E-2
JF  - Biomedicines
N2  - Macrophages in pathologically expanded dysfunctional white adipose tissue are exposed to a mix of potential modulators of inflammatory response, including fatty acids released from insulin-resistant adipocytes, increased levels of insulin produced to compensate insulin resistance, and prostaglandin E-2 (PGE(2)) released from activated macrophages. The current study addressed the question of how palmitate might interact with insulin or PGE(2) to induce the formation of the chemotactic pro-inflammatory cytokine interleukin-8 (IL-8). Human THP-1 cells were differentiated into macrophages. In these macrophages, palmitate induced IL-8 formation. Insulin enhanced the induction of IL-8 formation by palmitate as well as the palmitate-dependent stimulation of PGE(2) synthesis. PGE(2) in turn elicited IL-8 formation on its own and enhanced the induction of IL-8 release by palmitate, most likely by activating the EP4 receptor. Since IL-8 causes insulin resistance and fosters inflammation, the increase in palmitate-induced IL-8 formation that is caused by hyperinsulinemia and locally produced PGE(2) in chronically inflamed adipose tissue might favor disease progression in a vicious feed-forward cycle.
KW  - macrophages
KW  - insulin
KW  - prostaglandin E-2
KW  - interleukin-8
KW  - inflammation
Y1  - 2021
U6  - https://doi.org/10.3390/biomedicines9050449
SN  - 2227-9059
VL  - 9
IS  - 5
PB  - MDPI
CY  - Basel
ER  -