Thus, our results verified the co-occurrence of RA and periodontal inflammation using experimental mouse models of RA, suggesting that iNAMPT in PDL cells plays a pivotal role in the pathogenesis of RA-mediated periodontal inflammation by regulating the expression levels of catabolic genes, such as IL6, IL8, CCL5, COX-2, MMP1, and MMP3.
In vitro, primary RA fibroblast-like synoviocytes (FLSs) expressed minimal TSP-1 mRNA levels with high transcript levels of NR4A2, vascular endothelial growth factor (VEGF), and IL-8 measured.
Interestingly, TNF-α has a feedback regulation with TLR5 expression in RA monocytes, whereas expression of this receptor is regulated by IL-17 and IL-8 in RA macrophages and fibroblasts.
However, because IKK-2 regulates the expression of other inflammatory cytokines (IL-1beta, IL-6, and IL-8), VEGF, and MMPs 1, 2, 3, and 13, which are involved in the inflammatory, angiogenic, and destructive processes in the RA joint, it may still be a good therapeutic target.
We found evidence that the IL-10 expression was functionally relevant, as neutralization of endogenously produced IL-10 in the RA synovial membrane cultures resulted in a two- to threefold increase in the protein levels of proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and IL-1 beta, although IL-6 and IL-8 levels were not affected.
These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis, tumor growth, and wound repair.
Whereas CREB inhibitors have off target effects and increased LPA-mediated IL-8 secretion, the silencing of CREB1 with short hairpin RNA significantly reduced LPA-induced chemokine production in RAFLS.
Importantly, M2 macrophages derived from HD or patients with RA showed both a decreased ratio of interleukin (IL)-10/IL-6 and IL-10/IL-8 upon stimulation with TLR2 ligand Pam3 compared with TLR4 ligand LPS.
No relation of miR-124 expression to measures of RA activity (DAS28 score; TSS), auto-antibodies (anti-CCP, RF, RF IgG, RF IgA, RF IgM), acute inflammatory markers (CRP, IL-6), and other cytokine and chemokines (IL-13, IL-15, IL-8, TNF-α, MCP-1, RANTES) was observed.
The production of inflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)- 6, and IL-8, was reduced by carvacrol in LPS-induced RA-FLSs.
The stimulation with resistin increased the protein levels of CXCL8 and CCL2 produced by RA FLSs, and the upregulated expression of CXCL8 was inhibited by the abrogation of CAP1 by siRNA for CAP1.
Transgenic overexpression of CLU in RA FLS promoted apoptosis within 24 h. We observed that CLU knockdown with small interfering RNA promoted IL-6 and IL-8 production.
TNF-induced mRNA stabilization in RA FLS occurs during the late phase of TNF response, is MAPK-dependent, and involves several genes with pathogenic potential such as IL6, CXCL1, CXCL3, CXCL8/IL8, CCL2, and PTGS2.
Inhibition of NF-kappaB activation significantly reduced the spontaneous and IL-1beta-induced secretion of IL-6 and IL-8 by RA FLS and the IL-1ss-induced production of IL-6 and IL-8 by human dermal fibroblasts.
The repertoires of proinflammatory cytokines/chemokines expressed by SpA and RA SFMC were very similar: monocyte chemotractant protein 1 (MCP-1), interleukin 8 (IL-8), IL-1beta, endothelial-monocyte activating polypeptide II, interferon-gamma, and tumor necrosis factor-alpha.MCP-1 was highly expressed in SpA SFMC.
We compared therefore an innate gene signature of Toll-like receptors (TLRs), seven key members of the interleukin (IL)1/IL1R family, and CXCL8/IL8 in peripheral blood mononuclear cells from well-defined patients with active stages of RA (<i>n</i> = 36, DAS28 ≥ 3.2), SLE (<i>n</i> = 28, SLEDAI > 6), and SSc (<i>n</i> = 22, revised EUSTAR index > 2.25).
IL-6 and IL-8 mRNA expressions in RA-FLS were evaluated by real-time PCR after pre-incubation with IL-29 and subsequent stimulation with peptidoglycan (PGN, TLR2 ligand), or polycytidylic acid (poly(I:C), TLR3 ligand), or lipopolysaccharide (LPS, TLR4 ligand) .
Interestingly, 5-azadC treatment up-regulated the SFRP2 expression, inhibited the FLS proliferation, suppressed the expression of IL-6 and IL-8 and the fibronectin production, suggesting that the decreased SFRP2 in RA model rats was due to the DNA methylation.