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Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis.

Xu L, Peng Q, Xuan W, Feng X, Kong X, Zhang M, Tan W, Xue M, Wang F - Mediators Inflamm. (2016)

Bottom Line: The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA.Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium.Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

ABSTRACT
We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.

No MeSH data available.


Related in: MedlinePlus

Immunostaining for IL-28Rα in OA fibroblasts and viability of OA FLS in response to IL-29. The expression of IL-28Rα in OA FLS, detected by immunofluorescent staining (a) and flow cytometric analysis (b). The magnification in (a) was ×400. (c) OA FLS viability after being incubated with IL-29 at 1, 10, and 100 ng/mL for 72 h was measured by MTT assay. The data present the mean ± SEM of three independent experiments.
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fig3: Immunostaining for IL-28Rα in OA fibroblasts and viability of OA FLS in response to IL-29. The expression of IL-28Rα in OA FLS, detected by immunofluorescent staining (a) and flow cytometric analysis (b). The magnification in (a) was ×400. (c) OA FLS viability after being incubated with IL-29 at 1, 10, and 100 ng/mL for 72 h was measured by MTT assay. The data present the mean ± SEM of three independent experiments.

Mentions: Immunofluorescence staining showed that IL-28Ra was expressed in OA FLS (Figures 3(a) and 3(b)), implying that OA FLS may be the important target of IL-29. IL-29 at 1, 10, and 100 ng/mL did not affect the viability of OA FLS after 72 h treatment (Figure 3(c)). Therefore, these doses were chosen for further experiments.


Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis.

Xu L, Peng Q, Xuan W, Feng X, Kong X, Zhang M, Tan W, Xue M, Wang F - Mediators Inflamm. (2016)

Immunostaining for IL-28Rα in OA fibroblasts and viability of OA FLS in response to IL-29. The expression of IL-28Rα in OA FLS, detected by immunofluorescent staining (a) and flow cytometric analysis (b). The magnification in (a) was ×400. (c) OA FLS viability after being incubated with IL-29 at 1, 10, and 100 ng/mL for 72 h was measured by MTT assay. The data present the mean ± SEM of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940582&req=5

fig3: Immunostaining for IL-28Rα in OA fibroblasts and viability of OA FLS in response to IL-29. The expression of IL-28Rα in OA FLS, detected by immunofluorescent staining (a) and flow cytometric analysis (b). The magnification in (a) was ×400. (c) OA FLS viability after being incubated with IL-29 at 1, 10, and 100 ng/mL for 72 h was measured by MTT assay. The data present the mean ± SEM of three independent experiments.
Mentions: Immunofluorescence staining showed that IL-28Ra was expressed in OA FLS (Figures 3(a) and 3(b)), implying that OA FLS may be the important target of IL-29. IL-29 at 1, 10, and 100 ng/mL did not affect the viability of OA FLS after 72 h treatment (Figure 3(c)). Therefore, these doses were chosen for further experiments.

Bottom Line: The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA.Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium.Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

ABSTRACT
We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.

No MeSH data available.


Related in: MedlinePlus