title: Transforming growth factor-β1 regulates human renal proximal tubular epithelial cell susceptibility to natural killer cells via modulation of the NKG2D ligands.
abstract: Transforming growth factor-β (TGF-β) has a significant role in the response to injury and tissue repair, and it has been detected in various cell types. However, the mechanism by which it regulates the response to ischemia‑reperfusion injury (IRI) and manipulates natural killer (NK) cells is not well understood. In the present study, TGF‑β modulated NK cell function, thereby promoting recovery from renal IRI. Human renal proximal tubular epithelial cells (HK‑2) treated with TGF‑β exhibited increased surface and intracellular expression of the NK group 2 member D (NKG2D) ligand MICA. This increased surface expression of MICA inhibited NK cell cytotoxicity to the HK‑2 cells. In addition, an enzyme‑linked immunosorbent assay revealed that TGF‑β treatment evidently increased the amount of soluble MICA released into the culture supernatant from HK‑2 cells. Taken together, these findings suggest that TGF‑β‑induced release of soluble MICA leads to downregulation of NKG2D, thereby preventing NK cell‑mediated cytotoxicity toward renal proximal tubular epithelial cells in renal IRI, which in turn improves the survival of these cells.
authors: Department of Microbiology and Immunology, Laboratory for Medical Oncology, Inje University College of Medicine, Busan 614‑735, Republic of Korea.
authors: Hyunkeun
authors: H
authors: Song
authors: Department of Microbiology and Immunology, Laboratory for Medical Oncology, Inje University College of Medicine, Busan 614‑735, Republic of Korea.
authors: Yeonye
authors: Y
authors: Kim
authors: Department of Anatomy, Inje University College of Medicine, Busan 614‑735, Republic of Korea.
authors: Gabin
authors: G
authors: Park
authors: Department of Anatomy, Inje University College of Medicine, Busan 614‑735, Republic of Korea.
authors: Yeong-Seok
authors: YS
authors: Kim
authors: Department of Anatomy, Inje University College of Medicine, Busan 614‑735, Republic of Korea.
authors: Seonghan
authors: S
authors: Kim
authors: Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614‑735, Republic of Korea.
authors: Hyun-Kyung
authors: HK
authors: Lee
authors: Department of Pediatrics, Inje University Busan Paik Hospital, Busan 614‑735, Republic of Korea.
authors: Woo Yeong
authors: WY
authors: Chung
authors: Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614‑735, Republic of Korea.
authors: Seok Ju
authors: SJ
authors: Park
authors: Department of Internal Medicine, Inje University Ilsan-Paik Hospital, Goyang, Gyeonggi 411‑706, Republic of Korea.
authors: Sang-Youb
authors: SY
authors: Han
authors: Department of Life Science, Sookmyung Women's University, Yongsan-ku, Seoul 140-742, Republic of Korea.
authors: Daeho
authors: D
authors: Cho
authors: Department of Anatomy, Inje University College of Medicine, Busan 614‑735, Republic of Korea.
authors: Daeyoung
authors: D
authors: Hur
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology*; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1