LAUSR

Luteolin inhibits the adhesion of neutrophils to microvascular endothelial cells and plays an important anti-inflammatory role, owing to its mechanism of suppressing the expression of lymphocyte function-associated antigen-1 (LFA-1) in the neutrophils. Our study deals with the different signaling pathways participating in LFA-1 expression in neutrophils along with the regulation of luteolin in order to elucidate new anti-inflammatory targets of luteolin, thus providing a basis for clinical applications. In our study, neutrophils were separated using density gradient centrifugation and the cAMP levels were determined using ELISA. Additionally, phosphorylation levels of p38 mitogen-activated protein kinase (MAPK), extracellular regulated protein kinase (ERK), phosphatidylinositol-3-kinase (PI3K), and Janus kinase (JAK) were also detected by Western blotting. LFA-1 expression was estimated using flow cytometry. The results showed that inhibiting agents used against p38 MAPK, ERK, PI3K, and JAK could significantly inhibit LFA-1 expression on neutrophils (p < 0.05, p < 0.01). Luteolin also induced a noteworthy elevation of cAMP in neutrophil supernatants (p < 0.01). It could also significantly inhibit ERK phosphorylation (p < 0.05, p < 0.01), and had no obvious effect on p38 MAPK phosphorylation in neutrophils (p > 0.05). However, phosphorylation of PI3K and JAK was not detected in neutrophils. To conclude, the p38 MAPK, ERK, PI3K, and JAK pathways are involved in the regulation of LFA-1 expression in neutrophils, and luteolin partially inhibits LFA-1 expression by increasing cAMP levels and suppressing ERK phosphorylation.