Olopatadine suppresses the migration of THP-1 monocytes induced by S100A12 protein.
Olopatadine hydrochloride (olopatadine) is an antiallergic drug with histamine H(1) receptor antagonistic activity. Recently, olopatadine has been shown to bind to S100A12 which is a member of the S100 family of calcium-binding proteins, and exerts multiple proinflammatory activities including chemotaxis for monocytes and neutrophils. In this study, we examined the possibility that the interaction of olopatadine with S100A12 inhibits the proinflammatory effects of S100A12. Pretreatment of olopatadine with S100A12 reduced migration of THP-1, a monocyte cell line, induced by S100A12 alone, but did not affect recombinant human regulated upon activation, normal T cell expressed and secreted (RANTES)-induced migration. Amlexanox, which also binds to S100A12, inhibited the THP-1 migration induced by S100A12. However, ketotifen, another histamine H(1) receptor antagonist, had little effect on the activity of S100A12. These results suggest that olopatadine has a new mechanism of action, that is, suppression of the function of S100A12, in addition to histamine H(1) receptor antagonistic activity.
Kishimoto
Kazuya
K
Pharmaceutical Research Center, Kyowa Hakko Kogyo Co, Ltd, Sunto-gun, Shizuoka, Japan.
Kaneko
Satoshi
S
Ohmori
Kenji
K
Tamura
Tadafumi
T
Hasegawa
Kazuhide
K
D000631:Aminopyridines / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods; D002465:Cell Movement; D003990:Dibenzoxepins / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation; D007665:Ketotifen / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology*; D000069605:Olopatadine Hydrochloride; D011969:Receptors, Histamine H1 / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism / Q000502:physiology*; D000067616:S100A12 Protein
D000631:Aminopyridines; D003990:Dibenzoxepins; D006634:Histamine H1 Antagonists; D039563:Histamine H1 Antagonists, Non-Sedating; D011969:Receptors, Histamine H1; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D000069605:Olopatadine Hydrochloride; C045742:amlexanox; D007665:Ketotifen