IL-1 receptor antagonist (IL-1RA) suppresses a hyper-IL-17 response-mediated bone loss in a murine experimental periodontitis

Zhang, Jinmei; Wang, Angela X; Wu, Yafei; Zhang, Shaoping

doi:10.1016/j.archoralbio.2022.105555

Cited by 5 publications

(5 citation statements)

References 63 publications

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“…No study has been found evaluating the effect of secukinumab on alveolar bone loss, so this study is the rst to evaluate the direct effect of secukinumab on alveolar bone loss. In experimental periodontitis studies, it has been shown that anti-IL-17 antibody administration reduces IL-17 levels and alveolar bone loss [27][28][29][30][31][32][33]. In this study, it was also observed that inhibiting IL-17 reduced alveolar bone loss.…”

Section: Discussionsupporting

confidence: 56%

Effects of IL-17 Inhibition with Secukinumab in Experimental Periodontitis

Taskin,

Aydinyurt,

Sancak

et al. 2023

Preprint

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Objective IL-17 plays a key role in the pathogenesis of periodontitis and systemic inflammatory diseases. This study investigates the effect of secukinumab, an IL-17 inhibitor, on the development of periodontal disease in a rat model of experimental periodontitis. Materials and Methods Experimental periodontitis was induced in rats by suturing silk around the mandibular first molar tooth (n = 32). After inducing periodontitis with ligature, the animals were divided into two groups: experimental and control. In the experimental group secukinumab was given intraperitoneally. The experiment was terminated 14 days after the induction of experimental periodontitis. Alveolar bone loss (ABL) was measured from microscope images, and the level of inflammatory cell infiltration (ICI) was analyzed by hematoxylin-eosin staining. IL-17, nuclear factor kappa B ligand receptor activator (RANKL), osteoprotegrin (OPG) levels and RANKL/OPG ratio were evaluated by immunohistochemistry. Results In the development process of experimental periodontitis, it was observed that the IL-17 inhibitor secukinumab decreased IL-17 levels, ABL, ICI and RANKL/OPG ratio (p < 0.05); and increased OPG levels (p < 0.05). No statistically significant effect of secukinumab application was observed on RANKL levels (p > 0.05). Conclusion The results obtained from this study suggested that inhibition of IL-17 with secukinumab slows down the development of periodontitis and IL-17 plays a key role as a pro-inflammatory cytokine in periodontitis pathogenesis. Clinical Relevance: This study is the first to examine the effect of secukinumab on periodontal tissues, despite of its limitations. It sheds light on the role of IL-17 in periodontal inflammation in experimental periodontitis.

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Section: Discussionsupporting

confidence: 56%

Effects of IL-17 Inhibition with Secukinumab in Experimental Periodontitis

Taskin,

Aydinyurt,

Sancak

et al. 2023

Preprint

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“…Similarly, the IL-1 receptor antagonist gene, IL1RN, encodes IL-Ra that inhibits IL-1B activity by competitive binding to IL-1 receptors [19][20][21][22], which acts as an anti-inflammatory cytokine and may even favour osteogenic differentiation of gingival-derived mesenchymal stem cells (GMSC) [21], also shows statistically significant down-regulated expression (p = 0.048) in the group of PD+IR+ patients. This result is especially interesting, since IL-1Ra has been described to protect GMSC cell viability and osteogenic capacity through the irruption of the NF-κB signaling pathway mediated by TLR-4 and activated by P. gingivalis-LPS [21].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, IL-1Ra is considered a strong defence against periodontitis, whose deficiency influences the most serious destruction of periodontal tissue in a murine experimental model of periodontitis [20]. Previous studies showed that mice without IL-1Ra have greater colonization of Aggregatibacter Actinomycetemcomitans, one of the bacteria most associated with incisor-molar [22] pattern periodontitis, formerly known as aggressive periodontitis, and from which patients with Down syndrome often suffer. Both are periodontal pathogenic bacteria, one of the most abundant species in the microbiome of Down syndrome patients compared to other patients with mental disabilities and periodontitis but who do not have Down syndrome, as reported by the systematic review and meta-analysis by Contaldo et al 2021 [5].…”

Section: Discussionmentioning

confidence: 99%

Retrospective Case-Control Study Genes Related to Bone Metabolism That Justify the Condition of Periodontal Disease and Failure of Dental Implants in Patients with down Syndrome

Baus-Domínguez

Gómez-Díaz

Torrés-Lagares

et al. 2023

IJMS

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Down syndrome patients show success rates in dental implants much lower than those observed in the general population. This retrospective case-control study aimed to identify possible genes that are related to the regulation of inflammatory responses and bone metabolism related to periimplantitis and implant loss, as well as genes related to bone quality. This process involved using the functional analysis of the gene expression software Transcriptome Analysis Console (TAC version 4.0 Applied BiosystemsTM, Thermo Fisher Scientific, Waltham, MA, USA) and a search for possible candidate genes involved. The focus was placed on the 93 genes related to periodontitis, periimplantitis, bone loss, implant loss, and genes related to bone quality and regulators underlying the establishment and maintenance of osseointegration. Five genes showed statistically significant results (p < 0.05) in our comparison. Four of them, IL1B (p = 0.023), IL1RN (p = 0.048), BGLAP (p = 0.0372) and PTK2 (p = 0.0075) were down-regulated in the periodontal disease and implant rejection group, and only one was overexpressed: FOXO1A (p = 0.0552). The genes with statistically significant alterations described in this article determine that the group of Down syndrome patients with periodontal disease and implant failure is a group of patients genetically susceptible to suffering from both conditions together.

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“…At one end, it can inhibit the pathogenic action of excess IL-1β, secreted by M. tb infected macrophages ( 67 ). At the other end, it can inhibit the conversion of Th1 cells into the pathogenic Th17.1 cells, by the combined action of IL-1β and TGF-β ( 68 ). IL-1β and TGF-β are the major polarizing cytokines for Th17 differentiation.…”

Section: T Cells As Mediators Of Dm-tb Synergymentioning

confidence: 99%

“…Upregulation of antigen presentation machinery, along with defective IL-1Ra secretion, indicates that, chronic diabetes might activate a dormant, pathogenic, autoreactive Th17.1 cells, which might promote LTBI reactivation and might also worsen active TB disease ( 73 ). Recently, pathogenic Th17.1 cells have been associated with poor prognosis in TB ( 68 ). However, whether chronic diabetes augments these cells needs to be tested.…”

Section: T Cells As Mediators Of Dm-tb Synergymentioning

confidence: 99%

Immune-endocrine network in diabetes-tuberculosis nexus: does latent tuberculosis infection confer protection against meta-inflammation and insulin resistance?

Aravindhan,

Yuvaraj

2024

Front. Endocrinol.

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Tuberculosis patients with diabetes, have higher sputum bacillary load, delayed sputum conversion, higher rates of drug resistance, higher lung cavitary involvement and extra-pulmonary TB infection, which is called as “Diabetes-Tuberculosis Nexus”. However, recently we have shown a reciprocal relationship between latent tuberculosis infection and insulin resistance, which has not been reported before. In this review, we would first discuss about the immune-endocrine network, which operates during pre-diabetes and incipient diabetes and how it confers protection against LTBI. The ability of IR to augment anti-TB immunity and the immunomodulatory effect of LTBI to quench IR were discussed, under IR-LTB antagonism. The ability of diabetes to impair anti-TB immunity and ability of active TB to worsen glycemic control, were discussed under “Diabetes-Tuberculosis Synergy”. The concept of “Fighter Genes” and how they confer protection against TB but susceptibility to IR was elaborated. Finally, we conclude with an evolutionary perspective about how IR and LTBI co-evolved in endemic zones, and have explained the molecular basis of “IR-LTB” Antagonism” and “DM-TB Synergy”, from an evolutionary perspective.

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IL-1 receptor antagonist (IL-1RA) suppresses a hyper-IL-17 response-mediated bone loss in a murine experimental periodontitis

Cited by 5 publications

References 63 publications

Effects of IL-17 Inhibition with Secukinumab in Experimental Periodontitis

Effects of IL-17 Inhibition with Secukinumab in Experimental Periodontitis

Retrospective Case-Control Study Genes Related to Bone Metabolism That Justify the Condition of Periodontal Disease and Failure of Dental Implants in Patients with down Syndrome

Immune-endocrine network in diabetes-tuberculosis nexus: does latent tuberculosis infection confer protection against meta-inflammation and insulin resistance?

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