Pro-inflammatory Cytokines Induce Suppressor of Cytokine Signaling-3 in Human Periodontal Ligament Cells

Fukushima, Akie; Kajiya, Hiroshi; Izumi, Toshio; Shigeyama, Chieko; Okabe, Koji; Anan, Hisashi

doi:10.1016/j.joen.2010.02.027

Cited by 26 publications

(24 citation statements)

References 32 publications

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“…The interference in toll-like receptors and interleukin-1 receptor downstream signaling pathways should be considered to control the development and progression of endodontic lesions. In the future, the use of the RNA interference can reduce the differentiation of macrophages into osteoclasts; the induction of cytosolic phospholipase-A (cPLA) and beta-defensin2; and, consequently, the release of TNF-a, IL-1b, and IL-6 (36)(37)(38). Another strategy is the superexpression of specific regulator proteins such as SOCS3, interferon-gamma, and interleukin-10 through local delivery of DNA vectors (39).…”

Section: S21mentioning

confidence: 99%

Antigenic Activity of Bacterial Endodontic Contents from Primary Root Canal Infection with Periapical Lesions against Macrophage in the Release of Interleukin-1β and Tumor Necrosis Factor α

Martinho

Chiesa

Leite

et al. 2010

Journal of Endodontics

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Section: S21mentioning

confidence: 99%

Antigenic Activity of Bacterial Endodontic Contents from Primary Root Canal Infection with Periapical Lesions against Macrophage in the Release of Interleukin-1β and Tumor Necrosis Factor α

Martinho

Chiesa

Leite

et al. 2010

Journal of Endodontics

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“…It has been shown that IL-1 is approximately 500-fold more potent than tumor necrosis factor in stimulating bone resorption (11). This could be because of the amount of expression of suppressors of cytokine signaling proteins (12, 13). …”

mentioning

confidence: 99%

Genetic Predisposition to Persistent Apical Periodontitis

Morsani

Aminoshariae

Han

et al. 2011

Journal of Endodontics

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Introduction The proinflammatory cytokine interleukin (IL)-1 is a key regulator of host responses to microbial infection and a major modulator of extracellular matrix catabolism and bone resorption. Allele2 of IL-1b is associated with a four-fold increase in IL-1β production. The aim of this case-control study was to evaluate the gene polymorphism of IL-1β in the pathogenesis of endodontic failure. We hypothesized that the gene polymorphism (allele2 of IL-1β) would influence host response and enhance inflammatory reactions predisposing to persistent apical periodontitis (PAP). Materials and Methods Subjects with at least 1 year of follow-up after root canal therapy (RCT) were recalled. Inclusion and exclusion criteria were applied, and 34 subjects with signs/symptoms of PAP with otherwise acceptable RCT were included. Sixty-one controls showed healing with acceptable RCT. Genomic DNA from buccal mucosa was amplified by polymerase chain reaction followed by restriction fragment length polymorphism to distinguish the alleles of IL-1β gene polymorphism. Results A significant difference in the distribution of the polymorphic genotype among cases (70.6%) and controls (24.6%) (P < .001, Pearson χ2) was shown. Conclusions These findings suggest that specific genetic markers associated with increased IL-1β production may contribute to increased susceptibility to PAP.

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“…Overexpression of SOCS3 in cell lines has shown that SOCS proteins can inhibit many cytokine-induced responses (23). For example, it has been reported that SOCS3 overexpression in human periodontal ligament (PDL) cells reduces the phosphorylation in downstream signaling molecules including STAT (40). Furthermore, enhanced SOCS3 gene expression has been found to promote IL-10 production, suggesting that STAT3 and SOCS3 may play an important role in regulation of cytokine-induced anti-inflammatory responses (41).…”

Section: Discussionmentioning

confidence: 99%

NDRG2-mediated Modulation of SOCS3 and STAT3 Activity Inhibits IL-10 Production

et al. 2010

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BackgroundN-myc downstream regulated gene 2 (NDRG2) is a member of the NDRG gene family. Our previous report indicated a possible role for NDRG2 in regulating the cytokine, interleukin-10 (IL-10), which is an important immunosuppressive cytokine. Several pathways, including p38-MAPK, NF-κB, and JAK/STAT, are used for IL-10 production, and the JAK/STAT pathway can be inhibited in a negative feedback loop by the inducible protein, SOCS3. In the present study, we investigated the effect of NDRG2 gene expression on IL-10 signaling pathway that is modulated via SOCS3 and STAT3.MethodsWe generated NDRG2-overexpressing U937 cell line (U937-NDRG2) and treated the cells with PMA to investigate the role of NDRG2 in IL-10 production. U937 cells were also transfected with SOCS3- or NDRG2-specific siRNAs to examine whether the knockdown of SOCS3 or NDRG2 influenced IL-10 expression. Lastly, STAT3 and SOCS3 induction was measured to identify the signaling pathway that was associated with IL-10 production.ResultsRT-PCR and ELISA assays showed that IL-10 was increased in U937-mock cells upon stimulation with PMA, but IL-10 was inhibited by overexpression NDRG2. After PMA treatment, STAT3 phosphorylation was decreased in a time-dependent manner in U937-mock cells, whereas it was maintained in U937-NDRG2 cells. SOCS3 was markedly reduced in U937-NDRG2 cells compared with U937-mock cells. IL-10 production after PMA stimulation was reduced in U937 cells when SOCS3 was inhibited, but this effect was less severe when NDRG2 was inhibited.ConclusionNDRG2 expression modulates SOCS3 and STAT3 activity, eventually leading to the inhibition of IL-10 production.

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Pro-inflammatory Cytokines Induce Suppressor of Cytokine Signaling-3 in Human Periodontal Ligament Cells

Cited by 26 publications

References 32 publications

Antigenic Activity of Bacterial Endodontic Contents from Primary Root Canal Infection with Periapical Lesions against Macrophage in the Release of Interleukin-1β and Tumor Necrosis Factor α

Antigenic Activity of Bacterial Endodontic Contents from Primary Root Canal Infection with Periapical Lesions against Macrophage in the Release of Interleukin-1β and Tumor Necrosis Factor α

Genetic Predisposition to Persistent Apical Periodontitis

NDRG2-mediated Modulation of SOCS3 and STAT3 Activity Inhibits IL-10 Production

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