title: Inhibitory action of roxithromycin on histamine release and prostaglandin D2 production from beta-defensin 2-stimulated mast cells.
abstract: The long-term, low-dose therapy with the 14-membered macrolides is well known to be effective for treatment of chronic airway inflammation. Although the mode of macrolides on neutrophils, monocytes, and epithelial cells has been investigated, the effect of macrolides on mast cell function is sparsely reported on. We first examined the effect of roxithromycin (RXM) on mast cell functions activated by human beta-defensin-2 (hBD-2). In this study, histamine release, prostaglandin D2 (PGD2) production, and intracellular Ca2+ concentration ([Ca2+]i) were measured in the absence and presence of RXM, using rat peritoneal mast cells stimulated with hBD-2. RXM, at doses of 12.5 and 25 microg/ml, significantly inhibited the histamine release from mast cells (p<0.05). In addition, PGD2 production induced by hBD-2 was significantly reduced by RXM at 6.25 (p<0.05) and 12.5 microg/ml (p<0.01). Furthermore, the hBD-2-induced increase of [Ca2+]i in mast cells was inhibited by 6.25 and 12.5 microg/ml of RXM (p<0.05). The present findings suggest that RXM modulates mast cell activation induced by hBD-2 via a Ca2+ signal pathway, thereby possibly alleviating chronic airway inflammation.
authors.affiliation: Department of Otorhinolaryngology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Kase
authors.forename: Jian
authors.initials: J
authors.lastname: Hua
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yokoi
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Ikeda
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015575:Roxithromycin / Q000494:pharmacology*; D013997:Time Factors; D023083:beta-Defensins / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; C106641:DEFB4A protein, human; D023083:beta-Defensins; D015575:Roxithromycin; D006632:Histamine; D015230:Prostaglandin D2; D002118:Calcium