The newly discovered cytokine IL-34 is expressed in gingival fibroblasts, shows enhanced expression by pro-inflammatory cytokines, and stimulates osteoclast differentiation

Abstract

Background: Interleukin-34 (IL-34) is a recently discovered cytokine functionally overlapping macrophage colony stimulating factor (M-CSF), a mediator of inflammation and osteoclastogenesis in bone-degenerative diseases such as rheumatoid arthritis. The objective of this study was to assess the expression of IL-34 in human gingival fibroblasts and investigate if the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and Interleukin-1B (IL-1β) modulate its expression, and moreover if IL-34 could contribute to recruitment of bone-resorbing osteoclasts. Methods: IL-34 expression was evaluated in gingival fibroblasts by real time PCR following stimulation by TNF-α, IL-1β, and treatment with inhibitors of intracellular pathways. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining of bone marrow macrophages treated with IL-34 or M-CSF in addition to receptor activator of nuclear factor kappa-B ligand (RANKL). Results: IL-34 was expressed in gingival fibroblasts. The expression was enhanced by TNF-α and IL-1β, regulated by the transcription factor nuclear factor kappa B (NF-κB) and activation of c-Jun N-terminal kinase (JNK). Further, IL-34 supports RANKL-induced osteoclastogensis of bone marrow macrophages, independently of M-CSF. Summary: In conclusion, this study shows for the first time IL-34 expression in human gingival fibroblasts, stimulated by TNF-α and IL-1β, key mediators of periodontal inflammation. Furthermore, IL-34 can be substituted for M-CSF in RANKL-induced osteoclastogenesis. IL-34 may contribute to inflammation and osteoclastogenesis in bone-degenerative diseases such as periodontitis. © 2013 Boström, Lundberg.