Inflammatory cytokines modulate eotaxin release by human lung fibroblast cell line.

Eotaxin, a potent eosinophil-specific chemotactic factor is increased in the lower respiratory tract of asthma patients. Recently, lung fibroblasts have been reported to produce eotaxin and their, activation can be modulated by inflammatory cytokines. To test the hypothesis that inflammatory cytokines modulate the eotaxin release from lung fibroblasts, top investigated the potential of interleukin-1 beta (IL-1 beta), turner necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN-gamma) to induce the release of eotaxin and eotaxin mRNA by the human fetal lung fibroblast tell line, HFL-1, was evaluated. HFL-1 released eotaxin constitutively without stimulation, but IL-1 beta or TNF-alpha stimulated eotaxin release in a dose- and time-dependent manner. IL-1 beta or TNF-alpha treatment of HFL-1 also resulted in the augmented expression of eotaxin mRNA. Although IFN-gamma alone had negligible effect on eotaxin release and mRNA expression, IFN-gamma induced a significant, concentration-dependent attenuation of eotaxin release and eotaxin mRNA expression from HFL-1 stimulated with IL-1 beta or TNF-alpha. These finding are consistent with the concept that lung fibroblast-derived eotaxin may in part be responsible for the eosinophil infiltration observed in the airways of asthmatic patients and that network of cytokines may modulate the eosinophil recruitment to the airways by stimulation of fibroblasts to release eotaxin.