IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
CERAMIDE 1-PHOSPHATE CONFERS ANTI-IN- FLAMMATORY AND TISSUE-REPAIR FUNCTIONS TO HUMAN MONOCYTES AND MACROPHAGES
Autor/es:
SCHATTNER MIRTA; ORTIZ WILCZYÑSKI, JUAN M.; NEGROTTO S; MENA HA; CARRERA SILVA EA
Lugar:
Buenos Aires
Reunión:
Congreso; Reunión Annual Conjunta SAIC-SAI-SAFIS 2020; 2020
Resumen:
Ceramide 1-Phosphate (C1P) is a bioactive sphingolipid released from dying cells and therefore highly augmented in damaged tis- sues. C1P exerts antiapoptotic effects in several cell types, and it is a well-known chemoattractant for macrophages and progenitor/ stem cells. It has been recently reported that C1P, in a murine model of hind limb ischemia, not only improved tissue regeneration by itself but also increased human endothelial colony forming cells (ECFC) regenerative properties. Considering that C1P levels are elevated at injured sites and its effects on human monocytes/macrophages (hMø) remained unknown, here we aimed to study whether C1P instructs these immune innate cells to enhance pro-resolving and repair functions. Human CD14+ monocytes were isolated from PB- MCs of healthy donors, cultured with RPMI+10% SFB and stimulated with different concentrations of C1P short chain analog C8-C1P (1 - 20μM). ANOVA, p≤0.05. We found that C8-C1P significantly pre- vented apoptosis of monocytes, and this effect was accompanied with a higher BCL-2 expression after 24 and 48h. Additionally, LPS and C8-C1P-treated monocytes showed lower expression levels of CD80 and CD44, and CD80 and HLA-DR after 24 and 48h, re- spectively. Interestingly, hMø differentiated with a higher (20μM) or a lower (1μM) concentration of C8-C1P upregulated genes related to tissue-repair and resolution of inflammation like VEGFA, MER and PPARG and downregulated IRF1, a pro-inflammatory signa- ture. Moreover, C8-C1P-differentiated hMø supernatants increased ECFC in vitro tubule formation only with 20μM, probably due to increased levels of proangiogenic secreted factors. In conclusion, C8-C1P not only augmented monocytes survival and reduced their activation, but also affected hMø differentiation by conferring them pro-resolving and tissue-repair functions. Our results highlight the therapeutic potential of C1P to improve wound healing.