MODULATION OF FIBRONECTIN AND TENASCIN PRODUCTION IN HUMAN BRONCHIAL EPITHELIAL-CELLS BY INFLAMMATORY CYTOKINES IN-VITRO

Fibronectin (Fn) and tenascin (Tn) are two major extracellular matrix glycoproteins participating in tissue morphogenesis and repair. The re gulation of their synthesis and deposition during airway inflammation and their possible contribution in asthma are poorly understood. In th is study, modulation of Fn and Tn production was investigated in trans formed human bronchial epithelial cells in culture. The cells were tre ated with interferon gamma (IFN-gamma), tumor necrosis factor alpha (T NF-alpha), a combination of these cytokines, interleukins 3 and 6 (IL- 3 and IL-6), granulocyte macrophage-colony stimulating factor (GM-CSF) , and a combination of IL-3 and IL-6 for 48 h. Immunofluorescence and immunoblotting methods with monoclonal antibodies to Fn and Tn antibod ies suggested the production of some Fn and Tn in the untreated cells. Fn was minimally induced in response to IFN-gamma and TNF-alpha, when compared with the untreated cells, whereas TNF-alpha and especially t he IFN-gamma plus TNP-alpha combination resulted in a prominent Tn ind uction. Interleukins and GM-CSF did not induce Fn or Tn in any case. T hese results show that human bronchial epithelial cells are capable of producing Fn and Tn. The modulation of Fn and Tn may have an importan t impact on the pathology of epithelial cells during airway inflammati on in vivo.