title: Angiogenin reduces immune inflammation via inhibition of TANK-binding kinase 1 expression in human corneal fibroblast cells.
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.
authors.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.
authors.forename: Seung Hoon
authors.identifier: 0000-0002-0732-1611
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, 224-1 Heukseok-dong, Dongjak-Gu, Seoul 156-755, Republic of Korea.
authors.forename: Kyoung Woo
authors.identifier: 0000-0002-1181-5112
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Chungbuk National University, 52 Naesudong-ro, Heungdeok-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Kyong-Mi
authors.initials: KM
authors.lastname: Min
authors.affiliation: Department of Biochemistry, Chungbuk National University, 52 Naesudong-ro, Heungdeok-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Kyu-Wan
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Chungbuk National University, 52 Naesudong-ro, Heungdeok-gu, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Soo-Ik
authors.initials: SI
authors.lastname: Chang
authors.affiliation: Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, 224-1 Heukseok-dong, Dongjak-Gu, Seoul 156-755, Republic of Korea.
authors.forename: Jae Chan
authors.identifier: 0000-0002-0084-0793
authors.initials: JC
authors.lastname: Kim
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003315:Cornea / Q000166:cytology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; C046366:angiogenin; D012259:Ribonuclease, Pancreatic