title: Epigallocatechin gallate, a potential immunomodulatory agent of tea components, diminishes cigarette smoke condensate-induced suppression of anti-Legionella pneumophila activity and cytokine responses of alveolar macrophages.
abstract: Even though cigarette smoking has been shown to suppress immune responses in the lungs, little is known about the effect of cigarette smoke components on respiratory infections. In the present study, the effects of cigarette smoke condensate (CSC) on bacterial replication in alveolar macrophages and the immune responses of macrophages to infection were examined. Furthermore, a possible immunotherapeutic effect of epigallocatechin gallate (EGCg), a major form of tea catechins, on the CSC-induced suppression of antimicrobial activity and immune responses of alveolar macrophages was also determined. The treatment of murine alveolar macrophage cell line (MH-S) cells with CSC significantly enhanced the replication of Legionella pneumophila in macrophages and selectively down-regulated the production of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) induced by bacterial infection. The treatment of macrophages with EGCg not only overcame the CSC-induced suppression of antimicrobial activity but also strengthened the resistance of macrophages to infection. EGCg also markedly up-regulated the CSC-suppressed IL-6 and TNF-alpha production by macrophages in response to infection. The results of exogenous TNF-alpha treatment and neutralization treatment with anti-TNF-alpha and anti-gamma-interferon (IFN-gamma) antibodies and the determination of IFN-gamma mRNA levels indicate that CSC-suppressed macrophages can be activated by EGCg to inhibit L. pneumophila growth by up-regulation of TNF-alpha and IFN-gamma production. Thus, this study revealed that CSC selectively alters the immune responses of macrophages to L. pneumophila infection and leads to an enhancement of bacterial replication in macrophages. In addition, the tea catechin EGCg can diminish such suppressive effects of CSC on alveolar macrophages.
authors.affiliation: Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa, Florida 33612-4799, USA.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Klein
authors.forename: Herman
authors.initials: H
authors.lastname: Friedman
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007108:Immune Tolerance / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects*; D016952:Legionella pneumophila / Q000187:drug effects / Q000254:growth & development; D007877:Legionnaires' Disease / Q000188:drug therapy / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D010936:Plant Extracts; D012906:Smoke; D002392:Catechin; C045651:epigallocatechin gallate