Modulação da ativação de monócitos por lipoxinas

Abstract

Lipoxins (LXs) are arachidonic acid metabolites with well recognized anti-inflammatory and pro-resolution activities. Despite the large number of studies describing the role of LXs and their analogs in leukocytes and other cell types involved in inflammatory diseases, little is known about the mechanisms of action that trigger these responses. This work investigated the role of 15-epi-16-(para-fluoro)-phenoxy-lipoxin A4 (ATL-1), a synthetic analog of 15-epi-lipoxin A4 on various processes of monocyte activation. We characterized, for the first time, the lipoxin A4 receptor (ALX) in the monocytic lineage U937, through the assessment of its gene expression and protein and its functionality through the activation of ERK-2, which makes this cell line a suitable tool to study the mechanisms of action of LXs and their analogs on the monocytes. Furthermore, we demonstrated that ATL-1 increases the expression of the enzyme heme oxygenase (HO)-1 in the U937 cells via activation of p38 MAP kinase (MAPK) and decreases the secretion of Monocyte chemoattractant protein-1 (MCP-1), a chemokine involved in the recruitment of monocytes to the inflammatory focus in LPS-stimulated U937 cells. MCP-1 secretion inhibition by ATL-1 was reverted by SB203580 indicating that this effect is dependent on the activation of p38 MAPK pathway. This study clarifies some of the mechanisms involved in the activation of monocytes by lipoxins which may lead to new approaches for the control of different pathologies where the inflammatory component is relevant