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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

Effect of IL-29 on the phosphorylation of Jak-STAT, AKT, MAPK, and NF-κB signaling pathways. OA FLS were treated with IL-29 at 100 ng/mL for 0 , 20, 40, and 60 min, and the activation of STAT 1/2/3/4/5/6, AKT, JNK, ERK, P38, p65, and NF-κB was evaluated by western blot. The relative quantification of target proteins was calculated by comparison of the bands density levels between samples. The results were expressed as mean ± SEM from three independent experiments. ∗P < 0.05 versus nontreatment group.
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fig6: Effect of IL-29 on the phosphorylation of Jak-STAT, AKT, MAPK, and NF-κB signaling pathways. OA FLS were treated with IL-29 at 100 ng/mL for 0 , 20, 40, and 60 min, and the activation of STAT 1/2/3/4/5/6, AKT, JNK, ERK, P38, p65, and NF-κB was evaluated by western blot. The relative quantification of target proteins was calculated by comparison of the bands density levels between samples. The results were expressed as mean ± SEM from three independent experiments. ∗P < 0.05 versus nontreatment group.

Mentions: OA FLS were stimulated with IL-29 and the activation of downstream signal transduction pathways including canonical Jak-STAT and noncanonical MAPK, AKT, and NF-κB pathways was evaluated (Figure 6). Following stimulation of OA FLS for 20 min, 40 min, and 60 min with IL-29 (100 ng/mL), phosphorylation of STAT 1 (Tyr701) and STAT 5 (Tyr694); JNK, ERK, and P38; and P65 and IκκB was significantly increased when compared to nontreatment controls. No change in phosphorylation of STATs 2 (Tyr690), 3 (Tyr705), and 6 (Tyr641) and AKT was observed in response to IL-29. Phosphorylation of STAT 3 (Ser727) and STAT 4 (Tyr693) was not detectable in OA FLS.


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)

Effect of IL-29 on the phosphorylation of Jak-STAT, AKT, MAPK, and NF-κB signaling pathways. OA FLS were treated with IL-29 at 100 ng/mL for 0 , 20, 40, and 60 min, and the activation of STAT 1/2/3/4/5/6, AKT, JNK, ERK, P38, p65, and NF-κB was evaluated by western blot. The relative quantification of target proteins was calculated by comparison of the bands density levels between samples. The results were expressed as mean ± SEM from three independent experiments. ∗P < 0.05 versus nontreatment group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Effect of IL-29 on the phosphorylation of Jak-STAT, AKT, MAPK, and NF-κB signaling pathways. OA FLS were treated with IL-29 at 100 ng/mL for 0 , 20, 40, and 60 min, and the activation of STAT 1/2/3/4/5/6, AKT, JNK, ERK, P38, p65, and NF-κB was evaluated by western blot. The relative quantification of target proteins was calculated by comparison of the bands density levels between samples. The results were expressed as mean ± SEM from three independent experiments. ∗P < 0.05 versus nontreatment group.
Mentions: OA FLS were stimulated with IL-29 and the activation of downstream signal transduction pathways including canonical Jak-STAT and noncanonical MAPK, AKT, and NF-κB pathways was evaluated (Figure 6). Following stimulation of OA FLS for 20 min, 40 min, and 60 min with IL-29 (100 ng/mL), phosphorylation of STAT 1 (Tyr701) and STAT 5 (Tyr694); JNK, ERK, and P38; and P65 and IκκB was significantly increased when compared to nontreatment controls. No change in phosphorylation of STATs 2 (Tyr690), 3 (Tyr705), and 6 (Tyr641) and AKT was observed in response to IL-29. Phosphorylation of STAT 3 (Ser727) and STAT 4 (Tyr693) was not detectable in OA FLS.

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