title: Interleukin-4- and interleukin-13-enhanced transforming growth factor-beta2 production in cultured human bronchial epithelial cells is attenuated by interferon-gamma.
abstract: Cytokines derived from lymphocytes are believed to play key roles in a variety of diseases, including airway diseases such as asthma. The current study was designed to evaluate the hypothesis that cytokines derived from Th2 cells, interleukin (IL)-4 and IL-13, might contribute to tissue remodeling by modulating the production of transforming growth factor (TGF)-beta. In addition, the ability of interferon (IFN)-gamma, a cytokine derived from Th1 cells that can antagonize many effects of IL-4 and IL-13, was also assessed for its effects on TGF-beta production. IL-4 and IL-13 both stimulated production of TGF-beta2 release from human bronchial epithelial cells in a time- and concentration-dependent manner. Both with and without acidification, TGF-beta2 were detected. Neither TGF-beta1 nor TGF-beta3 was released. In contrast to the stimulatory effect on human bronchial epithelial cells, neither IL-4 nor IL-13 stimulated release of any TGF-beta isoform from human lung fibroblasts. IFN-gamma reduced both basal, IL-4-, and IL-13-stimulated release of TGF-beta2 in human bronchial epithelial cells. The stimulatory effects of IL-4 and IL-13 and the inhibitory effect of IFN-gamma on TGF-beta2 release were paralleled by mRNA levels, as assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). In summary, the Th2-derived cytokines, IL-4 and IL-13, can stimulate production of TGF-beta from airway epithelial cells but not from lung fibroblasts. IFN-gamma, in contrast, can inhibit TGF-beta2 release both under basal conditions and following IL-4 or IL-13 stimulation. The ability of these cytokines to modulate TGF-beta release may contribute to both normal airway repair and to the development of subepithelial fibrosis in asthma.
authors.affiliation: Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5125, USA.
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Wen
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kohyama
authors.forename: Xiangde
authors.initials: X
authors.lastname: Liu
authors.forename: Yun Kui
authors.initials: YK
authors.lastname: Zhu
authors.forename: Hangjun
authors.initials: H
authors.lastname: Wang
authors.forename: Hui Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Abe
authors.forename: John R
authors.initials: JR
authors.lastname: Spurzem
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D018793:Interleukin-13 / Q000378:metabolism / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D053781:Transforming Growth Factor beta2
chemical_list: D018793:Interleukin-13; D012333:RNA, Messenger; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D015847:Interleukin-4; D007371:Interferon-gamma