Stríz I, Mio T, Adachi Y, Carnevali S, Romberger D J, Rennard S I
Department of Immunology, Institute for CLinical and Experimental Medicine, Prague, Czech Republic.
Int J Immunopharmacol. 2000 Aug;22(8):573-85. doi: 10.1016/s0192-0561(00)00020-5.
Human bronchial epithelial cells are involved in airway immune mechanisms through secretion of cytokines and through cell-cell contacts with immunocompetent cells. The aim of our study was to assess the ability of interferon (IFN) alpha and gamma alone and in combination to modulate human bronchial epithelial cell (HBECs) release of the inflammatory cytokines IL-8 and IL-6 and fibronectin and to induce the surface expression of HLA-DR and ICAM-1 molecules involved in immune interactions with other cells. HBECs spontaneously secreted a limited amount of IL-8, which was significantly increased by IFN gamma. IFN alpha inhibited IFN gamma stimulated IL-8 secretion in a concentration-dependent manner. Further, IFN gamma induced IL-6 and fibronectin secretion, and this was also inhibited by IFN alpha. The expression of HLA-DR antigens was significantly increased by IFN gamma and partially inhibited by co-stimulation with IFN alpha. In contrast, IFN gamma also induced ICAM-1 expression by HBECs but co-stimulation with IFN alpha had no significant effect on the expression of this surface antigen. IFN alpha modulation of HBEC functions does not seem to be restricted to IFN gamma stimulation since either stimulatory or inhibitory effects of INF alpha on IL-8 production have been found in pilot experiments using IL-1 beta, TNF alpha, and TGF beta as stimuli. In summary, IFN-gamma induces a number of responses in HBECs including increased secretion of IL-6, IL-8 and fibronectin and increased expression of HLA-DR and ICAM-1. IFN alpha can inhibit all these except expression of ICAM-1 which is unaffected. IFN alpha can also interact with other inflammatory cytokines, but whether the effects are inhibitory or augmentive depends on the cytokines.
人支气管上皮细胞通过分泌细胞因子以及与免疫活性细胞的细胞间接触参与气道免疫机制。我们研究的目的是评估单独使用和联合使用干扰素（IFN）α和γ调节人支气管上皮细胞（HBECs）释放炎性细胞因子IL-8和IL-6以及纤连蛋白，并诱导参与与其他细胞免疫相互作用的HLA-DR和ICAM-1分子表面表达的能力。HBECs自发分泌少量IL-8，IFNγ可使其显著增加。IFNα以浓度依赖的方式抑制IFNγ刺激的IL-8分泌。此外，IFNγ诱导IL-6和纤连蛋白分泌，这也受到IFNα的抑制。IFNγ显著增加HLA-DR抗原的表达，而与IFNα共同刺激可部分抑制该表达。相反，IFNγ也诱导HBECs表达ICAM-1，但与IFNα共同刺激对该表面抗原的表达没有显著影响。IFNα对HBEC功能的调节似乎不限于IFNγ刺激，因为在以IL-1β、TNFα和TGFβ作为刺激物的初步实验中发现，INFα对IL-8产生既有刺激作用也有抑制作用。总之，IFN-γ在HBECs中诱导多种反应，包括IL-6、IL-8和纤连蛋白分泌增加以及HLA-DR和ICAM-1表达增加。IFNα可抑制除ICAM-1表达不受影响外的所有这些反应。IFNα还可与其他炎性细胞因子相互作用，但其作用是抑制性还是增强性取决于细胞因子。
