Differential Regulation of Eotaxin-1/CCL11 and Eotaxin-3/CCL26 Production by the TNF-α and IL-4 Stimulated Human Lung Fibroblast

Allergic asthma and allergic dermatitis are chronic inflammatory diseases and are characterized by an accumulation of eosinophils at sites of inflammation. Eotaxin-1/ CCL11 and eotaxin-3/CCL26 are members of the CC chernokine family, which are known to be potent chemoattractants for eosinophils. We observed that a hunran lung fibroblast, HFL-1 produces eotaxin-1 and -3 in response to TNF-α plus IL-4 stimulation, accompanied with NF-κB and STAT6 activation. We explored which signaling pathways are operative in the production of eotaxin-1 and -3 using several inhibitors. Eotaxin-1/CCL11 production was inhibited by a p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, but not by the MEK (MAPK/ERK kinase) inhibitors, PD98059 and U0126. In contrast, eotaxin-3/CCL26 production was inhibited similarly by PD98059 as well as U0126 and SB203580.