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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 of IL-29 and its receptor IL-28Rα in the peripheral blood mononuclear cells (PBMCs) and serum of OA patients. The mRNA levels of IL-29 (a) and IL-28Rα (b) in the OA PBMC (n = 30), when compared with that in HC PBMC (n = 30), were detected by real-time PCR. (c) The levels of IL-29 in the serum from OA patients (n = 30) and HC (n = 30) were assessed by ELISA. Data in graphs are the mean ± SEM.
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fig1: The expression of IL-29 and its receptor IL-28Rα in the peripheral blood mononuclear cells (PBMCs) and serum of OA patients. The mRNA levels of IL-29 (a) and IL-28Rα (b) in the OA PBMC (n = 30), when compared with that in HC PBMC (n = 30), were detected by real-time PCR. (c) The levels of IL-29 in the serum from OA patients (n = 30) and HC (n = 30) were assessed by ELISA. Data in graphs are the mean ± SEM.

Mentions: To investigate whether IL-29 was involved in the pathogenesis of OA, we first examined the expression of IL-29 mRNA and its receptor IL-28Ra in PBMC. Real-time PCR analysis revealed that mRNA expression of IL-29 and IL-28Ra was significantly higher in OA PBMCs when compared to HC (P = 0.0012 and 0.0017, resp.; Figures 1(a) and 1(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 of IL-29 and its receptor IL-28Rα in the peripheral blood mononuclear cells (PBMCs) and serum of OA patients. The mRNA levels of IL-29 (a) and IL-28Rα (b) in the OA PBMC (n = 30), when compared with that in HC PBMC (n = 30), were detected by real-time PCR. (c) The levels of IL-29 in the serum from OA patients (n = 30) and HC (n = 30) were assessed by ELISA. Data in graphs are the mean ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: The expression of IL-29 and its receptor IL-28Rα in the peripheral blood mononuclear cells (PBMCs) and serum of OA patients. The mRNA levels of IL-29 (a) and IL-28Rα (b) in the OA PBMC (n = 30), when compared with that in HC PBMC (n = 30), were detected by real-time PCR. (c) The levels of IL-29 in the serum from OA patients (n = 30) and HC (n = 30) were assessed by ELISA. Data in graphs are the mean ± SEM.
Mentions: To investigate whether IL-29 was involved in the pathogenesis of OA, we first examined the expression of IL-29 mRNA and its receptor IL-28Ra in PBMC. Real-time PCR analysis revealed that mRNA expression of IL-29 and IL-28Ra was significantly higher in OA PBMCs when compared to HC (P = 0.0012 and 0.0017, resp.; Figures 1(a) and 1(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