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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

The expression and cellular distribution of IL-29 and IL-28Rα in the synovial tissues. IL-29 and IL-28Rα in synovial tissues of OA patients (n = 5) and HC (n = 3) were detected by immunostaining (a) and semiquantification (b). Values in (b) are the mean ± SEM. ∗∗P < 0.01 versus medium control. (c) Colocalization of IL-29 with CD68 or FGF-2 in OA synovium was detected by double immunofluorescence staining, and nuclei were counterstained with DAPI. All of the magnification in this figure was ×400.
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fig2: The expression and cellular distribution of IL-29 and IL-28Rα in the synovial tissues. IL-29 and IL-28Rα in synovial tissues of OA patients (n = 5) and HC (n = 3) were detected by immunostaining (a) and semiquantification (b). Values in (b) are the mean ± SEM. ∗∗P < 0.01 versus medium control. (c) Colocalization of IL-29 with CD68 or FGF-2 in OA synovium was detected by double immunofluorescence staining, and nuclei were counterstained with DAPI. All of the magnification in this figure was ×400.

Mentions: Next, we assessed the expression and localization of IL-29 and IL-28Ra in synovial tissues from 5 OA patients and 3 HC with immunohistochemical analysis. As shown in Figure 2, IL-29 and IL-28Ra are strongly expressed in the lining layer of OA synovial tissues (Figure 2(a)), and semiquantitative analysis indicated that IL-29 and IL-28Ra were significantly increased in OA synovium compared to HC (P = 0.0045) (Figure 2(b)).


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)

The expression and cellular distribution of IL-29 and IL-28Rα in the synovial tissues. IL-29 and IL-28Rα in synovial tissues of OA patients (n = 5) and HC (n = 3) were detected by immunostaining (a) and semiquantification (b). Values in (b) are the mean ± SEM. ∗∗P < 0.01 versus medium control. (c) Colocalization of IL-29 with CD68 or FGF-2 in OA synovium was detected by double immunofluorescence staining, and nuclei were counterstained with DAPI. All of the magnification in this figure was ×400.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: The expression and cellular distribution of IL-29 and IL-28Rα in the synovial tissues. IL-29 and IL-28Rα in synovial tissues of OA patients (n = 5) and HC (n = 3) were detected by immunostaining (a) and semiquantification (b). Values in (b) are the mean ± SEM. ∗∗P < 0.01 versus medium control. (c) Colocalization of IL-29 with CD68 or FGF-2 in OA synovium was detected by double immunofluorescence staining, and nuclei were counterstained with DAPI. All of the magnification in this figure was ×400.
Mentions: Next, we assessed the expression and localization of IL-29 and IL-28Ra in synovial tissues from 5 OA patients and 3 HC with immunohistochemical analysis. As shown in Figure 2, IL-29 and IL-28Ra are strongly expressed in the lining layer of OA synovial tissues (Figure 2(a)), and semiquantitative analysis indicated that IL-29 and IL-28Ra were significantly increased in OA synovium compared to HC (P = 0.0045) (Figure 2(b)).

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