Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway

Min, Hong Ki; Won, Ji-Yeon; Bo-Mi, Kim; Lee, Kyung‐Ann; Lee, Seoung-Joon; Lee, Sang-Heon; Kim, Hae-Rim; Kim, Kyoung-Woon

doi:10.1186/s13075-020-02315-8

Cited by 32 publications

(28 citation statements)

References 26 publications

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“…As IL-22 is involved in the induction of inflammatory responses in other tissues, we investigated its effects on the production of inflammatory cytokines [ 41 , 51 ], and found that treatment of BV2 and HT22 cells with IL-22 increased the levels of TNF-α ( Figure 2 A) and IL-6 ( Figure S1 ). Previous studies have shown that binding of IL-22 to IL-22Rα induces the JAK1, STAT3, and STAT5 pathways, as well as the MAP kinase pathways [ 17 , 52 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

The Roles of IL-22 and Its Receptor in the Regulation of Inflammatory Responses in the Brain

Lee

et al. 2022

IJMS

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Interleukin (IL)-22 is a potent mediator of inflammatory responses. The IL-22 receptor consists of the IL-22Rα and IL-10Rβ subunits. Previous studies have shown that IL-22Rα expression is restricted to non-hematopoietic cells in the skin, pancreas, intestine, liver, lung, and kidney. Although IL-22 is involved in the development of inflammatory responses, there have been no reports of its role in brain inflammation. Here, we used RT-PCR, Western blotting, flow cytometry, immunohistochemical, and microarray analyses to examine the role of IL-22 and expression of IL-22Rα in the brain, using the microglial cell line, hippocampal neuronal cell line, and inflamed mouse brain tissue. Treatment of BV2 and HT22 cells with recombinant IL-22 increased the expression levels of the pro-inflammatory cytokines IL-6 and TNF-α, as well as cyclooxygenase (COX)-2 and prostaglandin E2. We also found that the JNK and STAT3 signaling pathways play an important role in IL-22-mediated increases in inflammatory mediators. Microarray analyses revealed upregulated expression of inflammation-related genes in IL-22-treated HT22 cells. Finally, we found that IL-22Rα is spontaneously expressed in the brain and is upregulated in inflamed mouse brain. Overall, our results demonstrate that interaction of IL-22 with IL-22Rα plays a role in the development of inflammatory responses in the brain.

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Section: Discussionmentioning

confidence: 99%

The Roles of IL-22 and Its Receptor in the Regulation of Inflammatory Responses in the Brain

Lee

et al. 2022

IJMS

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“…Also, IL-25 appears to be expressed by cells commonly found in atherosclerotic plaques such as endothelial cells, VSMCs, and macrophages (Mantani et al 2018a , b ). It has been reported that serum levels of IL-25 are significantly correlated with IL-22 in rheumatoid arthritis patients (Min et al 2020 ). Addition of IL-25 markedly reduces IL-22 expression but not changes mRNA levels of IL-22 receptors, IL-10RB and IL-22R1 (Min et al 2020 ), suggesting that the suppressive role of IL-25 on IL-22 expression is independent with IL-22 receptors.…”

Section: Negative Regulators Of Il-22 In Atherosclerosismentioning

confidence: 99%

“…It has been reported that serum levels of IL-25 are significantly correlated with IL-22 in rheumatoid arthritis patients (Min et al 2020 ). Addition of IL-25 markedly reduces IL-22 expression but not changes mRNA levels of IL-22 receptors, IL-10RB and IL-22R1 (Min et al 2020 ), suggesting that the suppressive role of IL-25 on IL-22 expression is independent with IL-22 receptors. Further studies showed that IL-25 also inhibits IL-22-induced STAT3 and p38 MAPK/IκBα pathway (Min et al 2020 ).…”

Section: Negative Regulators Of Il-22 In Atherosclerosismentioning

confidence: 99%

“…Addition of IL-25 markedly reduces IL-22 expression but not changes mRNA levels of IL-22 receptors, IL-10RB and IL-22R1 (Min et al 2020 ), suggesting that the suppressive role of IL-25 on IL-22 expression is independent with IL-22 receptors. Further studies showed that IL-25 also inhibits IL-22-induced STAT3 and p38 MAPK/IκBα pathway (Min et al 2020 ). Thus, upregulation of IL-25 may alleviate atherosclerosis by reducing IL-22 expression.…”

Section: Negative Regulators Of Il-22 In Atherosclerosismentioning

confidence: 99%

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Interleukin-22: a potential therapeutic target in atherosclerosis

Luo

Liu

et al. 2021

Mol Med

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Background Atherosclerosis is recognized as a chronic immuno-inflammatory disease that is characterized by the accumulation of immune cells and lipids in the vascular wall. In this review, we focus on the latest advance regarding the regulation and signaling pathways of IL-22 and highlight its impacts on atherosclerosis. Main body IL-22, an important member of the IL-10 family of cytokines, is released by cells of the adaptive and innate immune system and plays a key role in the development of inflammatory diseases. The binding of IL-22 to its receptor complex can trigger a diverse array of downstream signaling pathways, in particular the JAK/STAT, to induce the expression of chemokines and proinflammatory cytokines. Recently, numerous studies suggest that IL-22 is involved in the pathogenesis of atherosclerosis by regulation of VSMC proliferation and migration, angiogenesis, inflammatory response, hypertension, and cholesterol metabolism. Conclusion IL-22 promotes the development of atherosclerosis by multiple mechanisms, which may be a promising therapeutic target in the pathogenesis of atherosclerosis.

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“…IL-18BP (0, 10, 50, or 100 ng/mL) was also added three days after rhM-CSF stimulation to evaluate its effect on osteoclastogenesis. After 10-14 days of RANKL + M-CSF + IL-18BP or IL-17A + M-CSF + IL-18BP stimulation, tartrate-resistant acid phosphatase (TRAP)-positive cells were identified using a TRAP staining kit (Cosmo Bio, Tokyo, Japan), as described previously [20,21].…”

Section: Osteoclast Formationmentioning

confidence: 99%

IL-18 binding protein suppresses IL-17-induced osteoclastogenesis and rectifies type 17 helper T cell / regulatory T cell imbalance in rheumatoid arthritis

et al. 2021

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Background Patients with rheumatoid arthritis (RA) have increased levels of interleukin-18 (IL-18) and decreased levels of IL-18 binding protein (IL-18BP) in the serum and synovial fluid (SF) compared to those in patients with osteoarthritis (OA) or in healthy controls. In this study, we evaluated the effects of IL-18BP on osteoclastogenesis and T cell differentiation in RA in vitro. Methods Serum and SF of patients with RA and OA were collected to compare IL-18 and IL-18BP levels by the enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs) and SF mononuclear cells (SFMCs) of RA patients were cultured under type 17 helper T cell (Th17) polarisation conditions with or without IL-18BP. In addition, PBMCs were cultured in the presence of receptor activator of nuclear factor kappa-Β ligand (RANKL) or IL-17A with or without IL-18BP, and tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative polymerase chain reaction for expression levels of osteoclast-related genes were performed. Results IL-18 levels were higher in the serum and SF of patients with RA, whereas IL-18BP was lower in the SF of patients with RA than in the control group. Treatment of patients’ PBMCs with IL-18BP decreased the differentiation of CD4+ IL-17A+ and CD4+ RANKL+ T cells, whereas the differentiation of CD4+CD25highFOXP3+ T cell population increased in a dose-dependent manner. These changes in CD4+ T cell differentiation were also observed in the SFMCs of patients with RA. The levels IL-17A and soluble RANKL in the culture medium were significantly decreased by IL-18BP. IL-18BP administration decreased TRAP+ cell counts in a dose-dependent manner on the background of stimulation with RANKL-and IL-17A. In addition, expression levels of TRAP, NFATC1, CTSK, and TNFRSF11A (RANK) genes were lower in the IL-18BP treated cells. Conclusion We showed that IL-18BP can rectify the Th17/Treg imbalance and decrease IL-17-induced osteoclastogenesis in PBMCs from patients with RA. Therefore, IL-18BP may have therapeutic potential for RA treatment.

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Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway

Cited by 32 publications

References 26 publications

The Roles of IL-22 and Its Receptor in the Regulation of Inflammatory Responses in the Brain

The Roles of IL-22 and Its Receptor in the Regulation of Inflammatory Responses in the Brain

Interleukin-22: a potential therapeutic target in atherosclerosis

IL-18 binding protein suppresses IL-17-induced osteoclastogenesis and rectifies type 17 helper T cell / regulatory T cell imbalance in rheumatoid arthritis

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