IL-34 regulates IL-6 and IL-8 production in human lung fibroblasts via MAPK, PI3K-Akt, JAK and NF-κB signaling pathways.

IL-34 plays diverse roles in disease due to its inflammatory and immunosuppressive properties. Elevated IL-34 expression has been observed in lung cancers and pulmonary infections although its role is unclear. We found that IL-34 addition to primary lung fibroblasts significantly promoted IL-6 and IL-8 expression in a dose and time dependent manner. These effects were reversed when JAK, NF-κB, Akt and p38 inhibitors were included before IL-34 addition. Protein phosphorylation in these pathways was also observed through western-blotting. Stimulation of human lung fibroblasts with IL-34 in combination with TNF-α, IL-17A and IL-4 enhanced inflammatory cytokine production. Our data confirmed the inflammatory effect of IL-34 on human lung fibroblasts and suggested that the IL-34/CSF-1R axis may be a novel therapeutic target in pulmonary disease.