Interleukin-10 (IL-10) Inhibits Borrelia burgdorferi-Induced IL-17 Production and Attenuates IL-17-Mediated Lyme Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disorder affecting the synovial joints. The currently available drugs for RA are effective only in a proportion of patients and their prolonged use is associated with severe adverse effects. Thus, new anti-arthritic agents are being sought. We tested Pristimerin, a naturally occurring triterpenoid, for its therapeutic activity against rat adjuvant arthritis. Pristimerin effectively inhibited both arthritic inflammation and cartilage and bone damage in the joints. Pristimerin-treated rats exhibited a reduction in the pro-inflammatory cytokines (IL-6, IL-17, IL-18, and IL-23) and the IL-6/IL-17-associated transcription factors (pSTAT3 and ROR-γt), coupled with an increase in the immunomodulatory cytokine IL-10. Also increased was IFN-γ, which can inhibit IL-17 response. In addition, the Th17/Treg ratio was altered in favor of immune suppression and the RANKL/OPG ratio was skewed towards anti-osteoclastogenesis. This is the first report on testing Pristimerin in arthritis. We suggest further evaluation of Pristimerin in RA patients.

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“…Furthermore, IL-10 is known to be an immunomodulatory and anti-inflammatory cytokine [6,[42][43][44][45].…”

Section: Discussionmentioning

confidence: 99%

Pristimerin, a naturally occurring triterpenoid, protects against autoimmune arthritis by modulating the cellular and soluble immune mediators of inflammation and tissue damage

Nanjundaiah

Venkatesha

et al. 2014

Clinical Immunology

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“…For example, Il10 inhibits Ifng, Il2, and Il17 expression in mice (Hansen et al 2013). By contrast, mice lacking the ability to respond to Il10 present an increase in Ifng and Il17 levels (Gonzalez-Lombana et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…The downregulation of IL17 and IFNg expression in 6 h (reduced by approximately fivefold) could be due to an increase in the cytokine levels with an anti-inflammatory activity. For example, Il10 inhibits Ifng, Il2, and Il17 expression in mice (GonzalezLombana et al 2013, Hansen et al 2013.…”

Section: Discussionmentioning

confidence: 99%

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

Michailidis¹,

Anastasiadou²,

Guibert³

et al. 2014

Reproduction

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Sertoli cells (SCs) play an important physiological role in the testis, as they support, nourish, and protect the germ cells. As protection of the developing spermatozoa is an emerging aspect of reproductive physiology, this study examined the expression pattern of innate immune-related genes, including avian b-defensins (AvBDs), Toll-like receptors (TLRs), and cytokines, and investigated the time course of an inflammatory response in rooster SCs triggered by exposure to the bacterial endotoxin lipopolysaccharide (LPS). SCs were isolated from 6-week-old chicken, cultured in vitro, and stimulated with 1 mg/ml LPS at different time courses (0, 6, 12, 24, and 48 h). Data on expression analysis revealed that all ten members of the chicken TLR family, nine members of the AvBD family, as well as eight cytokine genes were expressed in SCs. Quantitative real-time PCR analysis revealed that LPS treatment resulted in significant induction of the expression levels of six TLRs, six AvBDs, and four cytokine genes, while two cytokine genes were downregulated and two other genes were unchanged. The increasing interleukin 1b (IL1b) production was confirmed in the conditioned medium. Furthermore, the phagocytosis of SCs was increased after LPS treatment. In conclusion, these findings provide evidence that SCs express innate immunerelated genes and respond directly to bacterial ligands. These genes represent an important component of the immune system, which could be integrated into semen, and present a distinctive constituent of the protective repertoire of the testis against ascending infections.

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“…Mavropoulos et al found that IL-10-producing B cells were impaired in psoriatic arthritis and inversely correlate with IL-17 and IFN- γ production [41]. Hansen et al noted that IL-10 regulated an arthritic IL-17 response following infection with Borrelia burgdorferi [42]. These results indicated that IL-10 could play a significant role in the immune control and regulate the immune responses of the other cytokines during Pneumocystis infection.…”

Section: Discussionmentioning

confidence: 99%

IL-17 Inversely Correlated with IL-10 via the STAT3 Gene in Pneumocystis-Infected Mice

Rong

Qian

Zhang

et al. 2019

Mediators of Inflammation

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Background. Pneumocystis pneumonia (PCP) remains a common opportunistic infection in immunosuppressed individuals. Current studies showed that multiple immune cells and cytokines took part in the host defense against Pneumocystis (PC). However, the roles of IL-17 and IL-10 in the development of PCP have not been elucidated. Methods. IL-10 and IL-17 levels in serum from PCP mice were detected via ELISA. The percentages of B10 cells, IL-10+ macrophages, and IL-10+ T cells in the lung from IL-17–/– PCP mice and Th17 cells and IL-17+γδT cells in IL-10–/– PCP mice were examined via flow cytometry. Also, antibody neutralization examination was also performed to elucidate the relationship of IL-17 and IL-10 in the PCP model. Results. We noted the increase of IL-17 and IL-10 levels in serum from mice infected with Pneumocystis. Furthermore, deficiency of IL-17 or IL-10 could lead to the delayed clearance of Pneumocystis and more severed lung damage. Our data also demonstrated that IL-17 deficiency enhanced the serum IL-10 level and the percentages of B10 cells, IL-10+ macrophages, and IL-10+ T cells in the lung from PCP mice. Interestingly, we also noted an increase of the IL-17 level in serum and Th17 cell and IL-17+γδT cell percentages in the lung from IL-10–/– PCP mice. Using antibody neutralization experiments, we found that the STAT3 gene might play a critical role in the interplay of IL-17 and IL-10 in PCP. Conclusion. Taken together, our results demonstrated that IL-17 and IL-10 could play the protective roles in the progression of PCP and the inverse correlation of them might be mediated by STAT3.

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Interleukin-10 (IL-10) Inhibits Borrelia burgdorferi-Induced IL-17 Production and Attenuates IL-17-Mediated Lyme Arthritis

Cited by 16 publications

References 54 publications

Pristimerin, a naturally occurring triterpenoid, protects against autoimmune arthritis by modulating the cellular and soluble immune mediators of inflammation and tissue damage

Pristimerin, a naturally occurring triterpenoid, protects against autoimmune arthritis by modulating the cellular and soluble immune mediators of inflammation and tissue damage

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

IL-17 Inversely Correlated with IL-10 via the STAT3 Gene in Pneumocystis-Infected Mice

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