Overexpression and Potential Regulatory Role of IL-17F in Pathogenesis of Chronic Periodontitis

Abstract

The objective of this study was to investigate the expression level, clinical significance, and possible regulating role of IL-17F in patients of chronic periodontitis. Periodontal local tissues were obtained from chronic periodontitis (CP) and healthy controls (HC) for real-time PCR (RT-PCR) detection with IL-17F and IL-17A messenger RNA (mRNA). Primary human gingival fibroblasts (HGF) were derived from patients receiving crown-lengthening procedures. Efficiency of small interfering RNA (siRNA) of IL-17R to HGF cells were assessed by Western blot and RT-PCR. Recombinant IL-17F and IL-17A were used to stimulate the HGF cells compared with the control group. Aspects of the nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK) signaling pathways were examined by Western blot. Production of pro-inflammatory cytokines induced by IL-17F and IL-17A was detected by RT-PCR. Statistical analysis was analyzed by SPSS software. It showed significantly elevated levels of IL-17F and IL-17A mRNA in CP gingival tissues compared with HC group (P<0.01). Further analysis showed a significant correlation between IL-17F and IL-17A mRNA in CP group (P<0.05), and both cytokines also correlated with the probing depth (P<0.05). Recombinant IL-17F can induce NF-κB phosphor-p65 and ERK phosphorylation of HGF cells similar to that of IL-17A. Interestingly, we found that both IL-17F and IL-17A could promote the important inflammatory cytokines IL-6, CXCL8, and CCL20 production compared with IL-17R siRNA group (P<0.05). This study indicates that IL-17F may be involved in pathogenesis of periodontitis like IL-17A. The role of IL-17F in disease pathogenesis needs to be further investigated.

Assessment of microRNA‐144‐5p and its putative targets in inflamed gingiva from chronic periodontitis patients

“…Thus, we propose that miR‐144‐5p might regulate the chronic periodontal inflammation progression via COX2 , IL17F or other autophagy‐related genes in the autophagy process. However, both COX2 and IL17F showed downregulated expression at the mRNA level in the chronic periodontitis group, which contradicted to previous results . The reason for different results in this study might be that, in our study, gingival tissues were collected after initial periodontal treatment and this could have an effect on the inflammation condition of the periodontium.…”

“…The genes encoding important molecules involved in periodontal inflammation identified in previously published articles include matrix metallopeptidases including MMP1 , MMP2 , MMP3 , MMP8 , MMP9 and MMP13 and tissue inhibitors of metalloproteinases including TIMP1 , TIMP3 and TIMP4 ; various interleukin (IL) families including IL1 β, IL2 , IL4 , IL6 , IL8 , IL10 , IL11 , IL 12 , IL17A , IL17F , IL18 , IL21 , IL23 and IL35 ; the pentraxin family including C‐reactive protein/pentraxin 1 ( CRP / PTX1 ) and pentraxin 3 ( PTX3 ); the TNF superfamily TNF‐ α and the receptor activator of the NFκB ligand/TNF superfamily member 11 ( RANKL / TNFSF11 ); the TNF receptor superfamily osteoprotegerin/TNF receptor superfamily member 11b ( OPG / TNFRSF11B ); the transforming growth factor (TGF) superfamily TGF β 1 ; the TLR family including TLR2 and TLR4 ; chemokines including C‐C motif chemokine ligands ( CCL2 , CCL3 , CCL5 , CCL19 , CCL20 ), C‐C motif chemokine receptor 4 ( CCR4 ) and C‐X‐C motif chemokine ligands ( CXCL6 , CXCL8 / IL8 ); suppressors of cytokine signalling including SOCS1 and SOCS3 ; interferon IFN‐ γ; transcription regulator T‐box 21 ( TBX21 ); NF κ B / NFKB1 ; TNF‐α‐induced protein 3 ( TNFAIP3 ); peptidylprolyl isomerase A/cyclophilin A ( PPIA / CypA ); and cyclooxygenase 2/prostaglandin‐endoperoxide synthase 2 ( COX2/PTGS2 ) . By combining the retrieval and computer algorithm prediction results, potential target genes related to periodontal inflammation were determined.…”

Role of distinct CD4+T helper subset in pathogenesis of oral lichen planus

“…The IL-6 expression was found in serum and saliva of OLP patients (51) and was considered indicative of a Th2 cellular involvement in OLP (22,42), which was involved in the initial reaction of OLP pathogenesis (1). Similarly, as an important NF-kappaB cytokine, IL-6 has been regarded as a bridge in linking inflammatory disease to cancer (52), which can be greatly induced by IL-17 family cytokines like IL-17A or IL-17F (53). Furthermore, we tested the NF-kappaB-associated pro-inflammatory cytokines in OLP patients and found IL-6, IL-8, and TNF-a all significantly increased in OLP salivary and serum (25,54).…”

Environmental lead effects on gene expression in oral epithelial cells

“…Previous studies have shown increased CCL20 expression by epithelial cells stimulated with P. intermedia , by P. gingivalis and F. nucleatum . This chemokine has also been documented in periodontitis tissues, with elevated levels linked to increased numbers of dendritic cells in diseased sites and elevations in expression of IL‐17‐related chemokines including CCL20 . IL‐23 activates STAT4 within the JAK‐STAT signaling cascade inducing interferon‐γ, preferentially targeting memory CD4 + T cells and promoting the production of various proinflammatory cytokines.…”

“…76 This chemokine has also been documented in periodontitis tissues, with elevated levels linked to increased numbers of dendritic cells in diseased sites 77 and elevations in expression of IL-17-related chemokines including CCL20. 78 IL-23 activates STAT4 within the JAK-STAT signaling cascade 79 inducing interferonγ, preferentially targeting memory CD4 + T cells and promoting the production of various proinflammatory cytokines. Information on this cytokine in periodontitis is rather limited, but may have a role in the cytokine cascade of granuloma tissues 80 and in responses of periodontal ligament cells to LPS.…”