TY - JOUR
T1 - Interleukin-4- and interleukin-13-enhanced transforming growth factor-β2 production in cultured human bronchial epithelial cells is attenuated by interferon-γ
AU - Wen, Fu Qiang
AU - Kohyama, Tadashi
AU - Liu, Xiangde
AU - Yun, Kui Zhu
AU - Wang, Hangjun
AU - Hui, Jun Kim
AU - Kobayashi, Tetsu
AU - Abe, Shinji
AU - Spurzem, John R.
AU - Rennard, Stephen I.
PY - 2002
Y1 - 2002
N2 - 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)-β. In addition, the ability of interferon (IFN)-γ, 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-β production. IL-4 and IL-13 both stimulated production of TGF-β2 release from human bronchial epithelial cells in a time- and concentration-dependent manner. Both with and without acidification, TGF-β2 were detected. Neither TGF-β1 nor TGF-β3 was released. In contrast to the stimulatory effect on human bronchial epithelial cells, neither IL-4 nor IL-13 stimulated release of any TGF-β isoform from human lung fibroblasts. IFN-γ reduced both basal, IL-4-, and IL-13-stimulated release of TGF-β2 in human bronchial epithelial cells. The stimulatory effects of IL-4 and IL-13 and the inhibitory effect of IFN-γ on TGF-β2 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-β from airway epithelial cells but not from lung fibroblasts. IFN-γ, in contrast, can inhibit TGF-β2 release both under basal conditions and following IL-4 or IL-13 stimulation. The ability of these cytokines to modulate TGF-β release may contribute to both normal airway repair and to the development of subepithelial fibrosis in asthma.
AB - 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)-β. In addition, the ability of interferon (IFN)-γ, 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-β production. IL-4 and IL-13 both stimulated production of TGF-β2 release from human bronchial epithelial cells in a time- and concentration-dependent manner. Both with and without acidification, TGF-β2 were detected. Neither TGF-β1 nor TGF-β3 was released. In contrast to the stimulatory effect on human bronchial epithelial cells, neither IL-4 nor IL-13 stimulated release of any TGF-β isoform from human lung fibroblasts. IFN-γ reduced both basal, IL-4-, and IL-13-stimulated release of TGF-β2 in human bronchial epithelial cells. The stimulatory effects of IL-4 and IL-13 and the inhibitory effect of IFN-γ on TGF-β2 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-β from airway epithelial cells but not from lung fibroblasts. IFN-γ, in contrast, can inhibit TGF-β2 release both under basal conditions and following IL-4 or IL-13 stimulation. The ability of these cytokines to modulate TGF-β release may contribute to both normal airway repair and to the development of subepithelial fibrosis in asthma.
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U2 - 10.1165/ajrcmb.26.4.4784
DO - 10.1165/ajrcmb.26.4.4784
M3 - Article
C2 - 11919085
AN - SCOPUS:0036009463
VL - 26
SP - 484
EP - 490
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 4
ER -