title: Antimicrobial and anti-inflammatory effects of clarithromycin on Mycobacterium avium complex replication in cultured human bronchial epithelial cells.
abstract: The Mycobacterium avium complex (MAC) invades cultured human bronchial cells, can replicate intracellularly, and facilitates the release of inflammatory cytokines and chemokines from cells. The purpose of this study was to examine the effects of clarithromycin (CAM) on MAC invasion, replication, and the release of cytokines and chemokines. A human bronchial epithelial cell line (BEAS-2B) monolayer grown on a tissue culture plate was infected with MAC. After 24 h, the cells were washed with Hanks' buffered salt solution, and extracellular bacteria were killed. The monolayer was further cultured for 5 days in medium containing CAM and subjected to a replication assay. The supernatants were assessed using a microchemotaxis assay and enzyme-linked immunosorbent assay (ELISA). mRNA expression was evaluated using a DNA array. The amount of intracellular MAC on day 5 of culture was significantly lower in the presence of CAM at the levels of 1× and 4× MIC. CAM inhibited the release of chemotactic activity and the production of interleukin (IL)-8 and macrophage chemotactic protein (MCP)-1. DNA array analysis of mRNA expression in BEAS-2B cells showed that CAM inhibited the expression of inflammatory cytokines and chemokines, involving IL-6, MCP-1, and IL-8 mRNA. MAC invaded and replicated in BEAS-2B cells and induced the production of chemotactic factors. In contrast, CAM may have bactericidal and bacteriostatic effects leading to the inhibition of inflammatory events.
authors.affiliation: Department of Infectious Diseases, Suzaka Hospital, 1332 Suzaka, Suzaka, 382-0091, Japan. yamazakiy@suzakahp.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Ushiki
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Sekiya
authors.initials: S
authors.lastname: Koyama
authors.forename: Keishi
authors.initials: K
authors.lastname: Kubo
mesh_terms: D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D017291:Clarithromycin / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism / Q000382:microbiology; D009000:Monocytes / Q000378:metabolism; D015269:Mycobacterium avium Complex / Q000187:drug effects*; D009504:Neutrophils / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D004269:DNA, Bacterial; D017291:Clarithromycin