We studied the effect of antiflammin-2 (AF-2) on adhesion molecule expression by HL-60 cells and endothelial (ECV304) cells stimulated by
lipopolysaccharides (LPSs), and on leukocyte-endothelial cell interaction in an in vitro coculture system. The action of
AF-2 on
prostanoid production in these experimental conditions was also tested. LPS increased the adhesion molecule expression, such as
lymphocyte function-associated antigen-1 and membrane attack complex-1 on HL-60 cells and
E-selectin and
intercellular adhesion molecule-1 on ECV304 cells. The LPS-stimulated adhesion molecule expression on HL-60/ECV304 coculture system was higher than on HL-60 or ECV304 cultures. LPS also induced HL-60 adhesion to ECV304 monolayer and
thromboxane B(2) and
prostaglandin E(2) (
PGE(2)) production in HL-60 culture and
PGE(2) in ECV304 culture.
Prostanoid production by HL-60/ECV304 cocultures was higher than by simple cultures.
AF-2 inhibited the enhancement of adhesion molecule expression induced by LPSs, especially
E-selectin. Thus,
AF-2 significantly reduced the HL-60 adhesion to endothelial cells stimulated by LPSs.
AF-2 also inhibited
prostanoid synthesis by ECV304 cells or HL-60/ECV304 coculture challenged by LPSs. In conclusion,
AF-2 reduced HL-60 adhesion to endothelial cells, suggesting that it reduces
inflammation by blocking leukocyte trafficking and the subsequent
eicosanoid production.