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Angiogenin reduces immune inflammation via inhibition of TANK-binding kinase 1 expression in human corneal fibroblast cells.

Lee SH, Kim KW, Min KM, Kim KW, Chang SI, Kim JC - Mediators Inflamm. (2014)

Bottom Line: Although ANG may be involved in the anti-inflammatory response, there is no evidence that it has direct anti-inflammatory effects.These findings suggest that ANG suppressed the TNF-α-induced inflammatory response in HCFs through inhibition of TBK1-mediated NF-κB nuclear translocation.These novel results are likely to play a significant role in the selection of immune-mediated inflammatory therapeutic targets and may shed light on the pathogenesis of immune-mediated inflammatory diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, 224-1 Heukseok-dong, Dongjak-Gu, Seoul 156-755, Republic of Korea ; Department of Medicine, Graduate School, Chung-Ang University, Seoul, Republic of Korea.

ABSTRACT
Angiogenin (ANG) is reportedly multifunctional, with roles in angiogenesis and autoimmune diseases. This protein is involved in the innate immune system and has been implicated in several inflammatory diseases. Although ANG may be involved in the anti-inflammatory response, there is no evidence that it has direct anti-inflammatory effects. In this study we sought to determine whether ANG has an anti-inflammatory effect in human corneal fibroblasts (HCFs) exposed to media containing tumor necrosis factor-alpha (TNF-α). We found that ANG reduced the mRNA expression of interleukin-1 beta (IL-1β), -6, -8 and TNF-α receptors (TNFR) 1 and 2. In contrast, ANG increased the mRNA expression of IL-4 and -10. Protein levels of TANK-binding kinase 1 (TBK1) were reduced by ANG in HCFs treated with TNF-α. Moreover, ANG diminished the expression of IL-6 and -8 and monocyte chemotactic protein- (MCP-) 1. The protein expression of nuclear factor-κB (NF-κB) was downregulated by ANG treatment. These findings suggest that ANG suppressed the TNF-α-induced inflammatory response in HCFs through inhibition of TBK1-mediated NF-κB nuclear translocation. These novel results are likely to play a significant role in the selection of immune-mediated inflammatory therapeutic targets and may shed light on the pathogenesis of immune-mediated inflammatory diseases.

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Related in: MedlinePlus

Real-time PCR analyses of proinflammatory cytokines and anti-inflammatory cytokines in HCFs. (a) The relative level of IL-1β, -6, and -8 mRNA was diminished by ANG treatment. ANG treatment alone did not affect the mRNA expression of proinflammatory cytokines. (b) The relative expression of IL-4 and -10 mRNA was increased by ANG treatment. ANG treatment alone increased the mRNA expression of IL-4 and -10. The experiments were performed in triplicate (*P < 0.05).
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fig1: Real-time PCR analyses of proinflammatory cytokines and anti-inflammatory cytokines in HCFs. (a) The relative level of IL-1β, -6, and -8 mRNA was diminished by ANG treatment. ANG treatment alone did not affect the mRNA expression of proinflammatory cytokines. (b) The relative expression of IL-4 and -10 mRNA was increased by ANG treatment. ANG treatment alone increased the mRNA expression of IL-4 and -10. The experiments were performed in triplicate (*P < 0.05).

Mentions: In order to determine whether ANG can reduce the inflammatory response in HCFs, TNF-α (20 ng/mL, 8 h) was added to the culture media and then cells were cultured in the presence or absence of ANG (2 μg/mL, 30 min). Real-time PCR was conducted to investigate the effects of ANG treatment on the mRNA expression of proinflammatory (IL-1β, -6, and -8) and anti-inflammatory cytokines (IL-4 and -10). The expression of proinflammatory cytokines (IL-1β, -6, and -8) induced by TNF-α treatment was reduced significantly in cells treated with ANG (Figure 1(a)). ANG treatment alone did not exert influence on the mRNA expression of proinflammatory cytokines. Moreover, the mRNA expression of anti-inflammatory cytokines (IL-4 and -10) was increased significantly after ANG treatment (Figure 1(b)). ANG treatment alone increased the mRNA expression of IL-4 and -10.


Angiogenin reduces immune inflammation via inhibition of TANK-binding kinase 1 expression in human corneal fibroblast cells.

Lee SH, Kim KW, Min KM, Kim KW, Chang SI, Kim JC - Mediators Inflamm. (2014)

Real-time PCR analyses of proinflammatory cytokines and anti-inflammatory cytokines in HCFs. (a) The relative level of IL-1β, -6, and -8 mRNA was diminished by ANG treatment. ANG treatment alone did not affect the mRNA expression of proinflammatory cytokines. (b) The relative expression of IL-4 and -10 mRNA was increased by ANG treatment. ANG treatment alone increased the mRNA expression of IL-4 and -10. The experiments were performed in triplicate (*P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4016892&req=5

fig1: Real-time PCR analyses of proinflammatory cytokines and anti-inflammatory cytokines in HCFs. (a) The relative level of IL-1β, -6, and -8 mRNA was diminished by ANG treatment. ANG treatment alone did not affect the mRNA expression of proinflammatory cytokines. (b) The relative expression of IL-4 and -10 mRNA was increased by ANG treatment. ANG treatment alone increased the mRNA expression of IL-4 and -10. The experiments were performed in triplicate (*P < 0.05).
Mentions: In order to determine whether ANG can reduce the inflammatory response in HCFs, TNF-α (20 ng/mL, 8 h) was added to the culture media and then cells were cultured in the presence or absence of ANG (2 μg/mL, 30 min). Real-time PCR was conducted to investigate the effects of ANG treatment on the mRNA expression of proinflammatory (IL-1β, -6, and -8) and anti-inflammatory cytokines (IL-4 and -10). The expression of proinflammatory cytokines (IL-1β, -6, and -8) induced by TNF-α treatment was reduced significantly in cells treated with ANG (Figure 1(a)). ANG treatment alone did not exert influence on the mRNA expression of proinflammatory cytokines. Moreover, the mRNA expression of anti-inflammatory cytokines (IL-4 and -10) was increased significantly after ANG treatment (Figure 1(b)). ANG treatment alone increased the mRNA expression of IL-4 and -10.

Bottom Line: Although ANG may be involved in the anti-inflammatory response, there is no evidence that it has direct anti-inflammatory effects.These findings suggest that ANG suppressed the TNF-α-induced inflammatory response in HCFs through inhibition of TBK1-mediated NF-κB nuclear translocation.These novel results are likely to play a significant role in the selection of immune-mediated inflammatory therapeutic targets and may shed light on the pathogenesis of immune-mediated inflammatory diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, 224-1 Heukseok-dong, Dongjak-Gu, Seoul 156-755, Republic of Korea ; Department of Medicine, Graduate School, Chung-Ang University, Seoul, Republic of Korea.

ABSTRACT
Angiogenin (ANG) is reportedly multifunctional, with roles in angiogenesis and autoimmune diseases. This protein is involved in the innate immune system and has been implicated in several inflammatory diseases. Although ANG may be involved in the anti-inflammatory response, there is no evidence that it has direct anti-inflammatory effects. In this study we sought to determine whether ANG has an anti-inflammatory effect in human corneal fibroblasts (HCFs) exposed to media containing tumor necrosis factor-alpha (TNF-α). We found that ANG reduced the mRNA expression of interleukin-1 beta (IL-1β), -6, -8 and TNF-α receptors (TNFR) 1 and 2. In contrast, ANG increased the mRNA expression of IL-4 and -10. Protein levels of TANK-binding kinase 1 (TBK1) were reduced by ANG in HCFs treated with TNF-α. Moreover, ANG diminished the expression of IL-6 and -8 and monocyte chemotactic protein- (MCP-) 1. The protein expression of nuclear factor-κB (NF-κB) was downregulated by ANG treatment. These findings suggest that ANG suppressed the TNF-α-induced inflammatory response in HCFs through inhibition of TBK1-mediated NF-κB nuclear translocation. These novel results are likely to play a significant role in the selection of immune-mediated inflammatory therapeutic targets and may shed light on the pathogenesis of immune-mediated inflammatory diseases.

Show MeSH
Related in: MedlinePlus