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- Boström, Elisabeth A., et al.
(author)
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The Newly Discovered Cytokine IL-34 Is Expressed in Gingival Fibroblasts, Shows Enhanced Expression by Pro-Inflammatory Cytokines, and Stimulates Osteoclast Differentiation
- 2013
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:12, s. e81665-
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Journal article (peer-reviewed)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-alpha) and Interleukin-1B (IL-1 beta) 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-alpha, IL-1 beta, 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-alpha and IL-1 beta, regulated by the transcription factor nuclear factor kappa B (NF-kappa B) 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-alpha and IL-1 beta, 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.
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