Cross-talk between TLR3 and TNF-α or IFN-γ Signaling in Induction of CXCL8/IL-8 and CXCL10/IP-10 Expression in Airway Epithelial Cells

CXCL8/IL-8 is a chemoattractant for neutrophils and mast cells, and regulates inflammatory cell recruitment in allergy, infection, and other neutrophil-related diseases. Interferon (IFN) -γ-inducible protein 10 (CXCL10/IP-10) is a chemokine that attracts mononuclear cells, Th1 cells, and natural killer cells. We investigated the levels of CXCL8/IL-8 and CXCL10/IP-10 expression by airway epithelial cells after exposure to the inflammatory cytokines tumor necrosis factor (TNF) -α and IFN-γ, and to poly I:C, a synthetic analog of double-stranded RNA that is a ligand of Toll-like receptor 3 (TLR3). Poly I:C, TNF-α, IFN-γ, and combinations of poly I:C with TNF-α or IFN-γ were used to stimulate the airway epithelial cell line BEAS-2B. Following stimulation, we determined CXCL8/IL-8 and CXCL10/IP-10 mRNA levels by real-time PCR and protein levels by ELISA. Poly I:C treatment upregulated mRNA and protein expression for both CXCL8/IL-8 and CXCL10/IP-10. The addition of TNF-α, but not IFN-γ, to poly I:C further increased the expression of CXCL8/IL-8 mRNA and protein. The addition of either TNF-α or IFN-γ to the poly I:C treatment further increased CXCL10/IP-10 mRNA and protein expression. Cross-talk between TLR3 signaling and inflammatory cytokines regulates the expression of CXCL8/IL-8 and CXCL10/IP-10 in airway epithelial cells. From our results, TNF-α and IFN-γ produce different effects on TLR3 signaling.