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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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Real-time PCR analysis of TNFR1 and 2 and TBK1 in HCFs. (a) The relative level of TNFR1 and 2 mRNA was diminished by ANG treatment. (b) The relative level of TBK1 mRNA was diminished by ANG treatment. The experiments were performed in triplicate (*P < 0.05).
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fig3: Real-time PCR analysis of TNFR1 and 2 and TBK1 in HCFs. (a) The relative level of TNFR1 and 2 mRNA was diminished by ANG treatment. (b) The relative level of TBK1 mRNA was diminished by ANG treatment. The experiments were performed in triplicate (*P < 0.05).

Mentions: Real-time PCR was performed to determine whether ANG decreases TBK1 and TNFR1 and 2. TNF-α treatment increased the mRNA expression of TNFR1 and 2, but a significant downregulation was noted after ANG treatment (Figure 3). ANG treatment alone did not affect the mRNA expression of TBK1 and TNFR1 and 2. Western blot analysis showed that ANG reduces the expression of TBK1. TNF-α treatment produced a dose-dependent increase in TBK1 phosphorylation and increased TBK1 expression. After ANG treatment, TBK1 expression was decreased (Figure 4). ANG treatment alone has little effect on the expression of TBK1.


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 analysis of TNFR1 and 2 and TBK1 in HCFs. (a) The relative level of TNFR1 and 2 mRNA was diminished by ANG treatment. (b) The relative level of TBK1 mRNA was diminished by ANG treatment. 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

fig3: Real-time PCR analysis of TNFR1 and 2 and TBK1 in HCFs. (a) The relative level of TNFR1 and 2 mRNA was diminished by ANG treatment. (b) The relative level of TBK1 mRNA was diminished by ANG treatment. The experiments were performed in triplicate (*P < 0.05).
Mentions: Real-time PCR was performed to determine whether ANG decreases TBK1 and TNFR1 and 2. TNF-α treatment increased the mRNA expression of TNFR1 and 2, but a significant downregulation was noted after ANG treatment (Figure 3). ANG treatment alone did not affect the mRNA expression of TBK1 and TNFR1 and 2. Western blot analysis showed that ANG reduces the expression of TBK1. TNF-α treatment produced a dose-dependent increase in TBK1 phosphorylation and increased TBK1 expression. After ANG treatment, TBK1 expression was decreased (Figure 4). ANG treatment alone has little effect on the expression of TBK1.

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