title: Bestatin, an inhibitor for aminopeptidases, modulates the production of cytokines and chemokines by activated monocytes and macrophages.
abstract: The aim of this study was to clarify the effect of bestatin, an aminopeptidase inhibitor, on the production of cytokines from peripheral blood monocytes and alveolar macrophages (AM). Human monocytes isolated from peripheral blood of healthy volunteers were incubated with or without lipopolysaccharide (LPS) in the presence or absence of bestatin. AM obtained from patients with sarcoidosis were incubated in the presence or absence of bestatin. The concentration of cytokines in the culture supernatant was determined by enzyme-linked immunosorbent assay. The expression of mRNA was determined by reverse transcription polymerase chain reaction. Bestatin suppressed the production and expression of proinflammatory cytokines and chemokines, interleukin (IL)-6, CXCL8/IL-8, CCL3/macrophage inflammatory protein (MIP)-1alpha by LPS-stimulated monocytes. The mean percentage of the inhibition of IL-6, CXCL8/IL-8, CCL3/MIP-1alpha by bestatin at a concentration of 50 microg/mL was 71.2%, 29.7% and 61.0%, respectively. On the other hand, bestatin increased the production and mRNA expression of IL-10 by LPS-stimulated monocytes. The treatment with bestatin significantly inhibited the production of IL-6 and CXCL8/IL-8 by AM from patients with sarcoidosis. The data presented here indicate that bestatin suppresses the production of the pro-inflammatory cytokines and stimulates the anti-inflammatory cytokine by activated human monocytes. This study suggests that bestatin may be useful as an anti-inflammatory agent in various inflammatory diseases.
authors.affiliation: Department of Internal Medicine and Molecular Therapeutics, Institute of Health Biosciences, The University of Tokushima Graduate School, 18-15 Kuramoto-cho 3, Tokushima 770-8503, Japan.
authors.forename: Battur
authors.initials: B
authors.lastname: Lkhagvaa
authors.forename: Kenji
authors.initials: K
authors.lastname: Tani
authors.forename: Keiko
authors.initials: K
authors.lastname: Sato
authors.forename: Yuko
authors.initials: Y
authors.lastname: Toyoda
authors.forename: Chiyuki
authors.initials: C
authors.lastname: Suzuka
authors.forename: Saburo
authors.initials: S
authors.lastname: Sone
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D011480:Protease Inhibitors; D012333:RNA, Messenger; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex