title: Erythromycin differentially inhibits lipopolysaccharide- or poly(I:C)-induced but not peptidoglycan-induced activation of human monocyte-derived dendritic cells.
abstract: Erythromycin (EM) has attracted attention because of its anti-inflammatory effect. Because dendritic cells (DCs) are the most potent APCs involved in numerous pathologic processes including innate immunity, we examined effects of EM on the activation of human DCs by pathogen-derived stimuli. Monocyte-derived DCs were pretreated with EM and subsequently stimulated with peptidoglycan, polyriboinosinic:polyribocytidylic acid (poly(I:C)), or LPS. The activation of DCs was assessed by surface molecule expression and cytokine production. To reveal the signaling pathways affected by EM, TLR expression, NF-kappaB, IFN regulatory factor-3, and AP-1 activation were examined. EM inhibited costimulatory molecule expression and cytokine production that was induced by poly(I:C) and LPS but not by peptidoglycan. EM pretreatment down- and up-regulated mRNA levels of TLR3 and TLR2, respectively, but did not affect that of TLR4. EM suppressed IFN regulatory factor-3 activation and IFN-beta production but not AP-1 activation induced by poly(I:C) and LPS. The inhibitory effect of EM on NF-kappaB activation was observed only in poly(I:C)-stimulated DCs. EM selectively suppressed activation of DCs induced by LPS and poly(I:C) in different ways, suggesting that the immuno-modulating effects of EM depend on the nature of pathogens. These results might explain why EM prevents the virus-induced exacerbation in the chronic inflammatory respiratory diseases and give us the clue to design new drugs to treat these diseases.
authors.affiliation: Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Yasutomi
authors.forename: Yusei
authors.initials: Y
authors.lastname: Ohshima
authors.forename: Nemuko
authors.initials: N
authors.lastname: Omata
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamada
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Urasaki
authors.forename: Mitsufumi
authors.initials: M
authors.lastname: Mayumi
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004336:Drug Antagonism; D004917:Erythromycin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology*; D011070:Poly I-C / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010457:Peptidoglycan; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D004917:Erythromycin; D011070:Poly I-C