Human Leukotactin‐1/CCL15 up‐regulates expression of cell adhesion molecules and stimulates monocyte adhesion to endothelial cells via JAK2/STAT3 signaling pathway

Abstract

Leukotactin‐1 (Lkn‐1)/CCL15 is a potent chemo‐attractant for leukocytes and endothelial cell and is implicated in inflammatory diseases. Lkn‐1/CCL‐15 enhances cell migration and activation of neutrophils and endothelial cells mainly through CCR1 signal pathway. We found that Lkn‐1/CCL15 significantly increased mRNA and protein expression of ICAM‐1 and VCAM‐1 compared with those in non‐stimulated endothelial cells. We showed that Lkn‐1/CCL15 increased cell adhesion of human U937 monocytoid cells to the endothelial cell. Furthermore, we provide evidence that Janus kinase (JAK) and STAT pathway plays a role in Lkn‐ 1/CCL15‐induced gene expression of cell adhesion molecules in endothelial cells. We observed that phosphorylation of JAK and STAT3 was stimulated after Lkn‐1/CCL15 treatment of HUVECs. Pretreatment of these cells with inhibitors for JAK, PI3K, and AKT prevented the Lkn‐1/CCL15‐induced expression of ICAM‐1, suggesting the involvement of JAK pathway in ICAM‐1 gene activation by Lkn‐1/CCL15. The results suggest that Lkn‐1/CCL15 and its signaling pathway may be a potential target for treating inflammatory diseases involving up‐regulation of cell adhesion molecules. .