Inflammatory cytokines modulate eotaxin release by human lung fibroblast cell line

Eotaxin, a potent eosinophil-specific chemotactic factor is increased in th e lower respiratory tract of asthma patients. Recently, lung fibroblasts ha ve been reported to produce eotaxin and their, activation can be modulated by inflammatory cytokines. To test the hypothesis that inflammatory cytokin es 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 eotax in and eotaxin mRNA by the human fetal lung fibroblast tell line, HFL-1, wa s evaluated. HFL-1 released eotaxin constitutively without stimulation, but IL-1 beta or TNF-alpha stimulated eotaxin release in a dose- and time-depe ndent manner. IL-1 beta or TNF-alpha treatment of HFL-1 also resulted in th e augmented expression of eotaxin mRNA. Although IFN-gamma alone had neglig ible effect on eotaxin release and mRNA expression, IFN-gamma induced a sig nificant, concentration-dependent attenuation of eotaxin release and eotaxi n mRNA expression from HFL-1 stimulated with IL-1 beta or TNF-alpha. These finding are consistent with the concept that lung fibroblast-derived eotaxi n may in part be responsible for the eosinophil infiltration observed in th e airways of asthmatic patients and that network of cytokines may modulate the eosinophil recruitment to the airways by stimulation of fibroblasts to release eotaxin.