Free Fatty Acid Receptor 1 Signaling Contributes to Migration, MMP-9 Activity, and Expression of IL-8 Induced by Linoleic Acid in HaCaT Cells
Free Fatty Acid Receptor 1 Signaling Contributes to Migration, MMP-9 Activity, and Expression of IL-8 Induced by Linoleic Acid in HaCaT Cells
Authors
Manosalva, Carolina
Alarcón, Pablo
Gonzalez, Karina
Soto, Jorge
Igor, Karin
Peña, Fernanda
Medina, Gustavo
Burgos, Rafael
Hidalgo, María A.
Alarcón, Pablo
Gonzalez, Karina
Soto, Jorge
Igor, Karin
Peña, Fernanda
Medina, Gustavo
Burgos, Rafael
Hidalgo, María A.
Authors
Date
Datos de publicación:
FRONTIERS IN PHARMACOLOGY, Vol. 55, N° 595, 2020
Keywords
Linoleic acid - Migration - Neutrophils - Keratinocytes (HaCaT) - Free fatty acids receptor 1 - Interleukin-8 - Matrix metalloproteinase-9
Collections
Abstract
Keratinocytes and neutrophils are the main cellular components in wound healing during re-epithelization and inflammation. Free fatty acids such as linoleic acid (LA) present beneficial properties for wound healing by modulating the inflammatory response. LA is a natural ligand of free fatty acids receptor 1 (FFA1), a G protein-coupled receptor (GPCR), able to modulate inflammatory process; however, the role of FFA1 in keratinocytes and wound healing remains poorly understood. In this study, we investigated the role of FFA1 signaling in migration, matrix metalloproteinase-9 (MMP-9) activity, and IL-8 expression induced by LA in keratinocytes. We confirmed that HaCaT cells, a human keratinocyte cell line, expresses the FFA1 receptor and GW1100, a selective antagonist of FFA1, decreased LA-induced migration of HaCaT cells. Also, GW9508, a synthetic agonist of FFA1, increased migration of these cells. Furthermore, ERK1/2 and p38 MAPK inhibitors abolished the LA-induced increase in cell migration. Besides, HaCaT cells stimulated with LA or GW9508 increased the activity of MMP-9 and the expression of IL-8. GW1100 partially inhibited both responses. We further evaluated the effects of HaCaT cells conditioned media stimulated with LA or GW9508 on neutrophil chemotaxis. Conditioned media induced neutrophil chemotaxis. Furthermore, IL-8 secreted by HaCaT cells stimulated with LA or GW9508, contributed to neutrophil chemotaxis. In conclusion, LA increased migration, MMP-9 activity, and expression of IL-8 from HaCaT cells via FFA1. Hence, these results showed that the effects induced by LA in keratinocytes can be mediated through FFA1, thus explaining a possible mechanism by which this fatty acid could accelerate wound healing.