title: Inhibition of human natural killer cell functional activity by human aspartyl β-hydroxylase.
abstract: Natural killer (NK) cells are a key component of the innate immune system and play pivotal roles as inflammatory regulators and in tumor surveillance. Human aspartyl β-hydroxylase (HAAH) is a plasma membrane and endoplasmic reticulum protein with hydroxylation activity, which is over-expressed in many malignant neoplasms and can be detected from the sera of tumor patients. HAAH is involved in regulating tumor cell infiltration and metastasis. Escaping from immune surveillance may help tumor cell infiltration and metastasis. However, the effects of HAAH on tumor immune surveillance have not yet been investigated carefully. The present study investigated the potential use of HAAH as an immune regulator of human NK cells. We assessed the effects of recombinant HAAH (r-HAAH) on primary human NK cell morphology, viability, cytotoxicity, apoptosis, receptors expression and cytokine/cytolytic proteins production. Our results demonstrated that r-HAAH negatively affects NK cell activity in a time and dose-dependent manner. It noticeably reduces the viability of the NK cells by increasing apoptosis and necrosis via caspase signaling pathways. Moreover, r-HAAH reduces the NK cell cytotoxicity by inhibiting surface expression of NKG2D, NKp44 and IFN-γ secretion. These findings suggest that one of the ways by which HAAH actively promotes tumor formation and proliferation is by inhibiting NK cell-surveillance activity.
authors.affiliation: Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 YouyiXilu, Xi'an 710072, Shaanxi, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Huyan
authors.affiliation: Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 YouyiXilu, Xi'an 710072, Shaanxi, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 YouyiXilu, Xi'an 710072, Shaanxi, PR China.
authors.forename: Lin-Jie
authors.initials: LJ
authors.lastname: Ye
authors.affiliation: Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 YouyiXilu, Xi'an 710072, Shaanxi, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 YouyiXilu, Xi'an 710072, Shaanxi, PR China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Xue
authors.affiliation: Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 YouyiXilu, Xi'an 710072, Shaanxi, PR China; Laboratory of Molecular Virology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, 1401 Rockville Pike, Rockville, MD, USA.
authors.forename: Ming-Jie
authors.initials: MJ
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 YouyiXilu, Xi'an 710072, Shaanxi, PR China.
authors.forename: Qing-Sheng
authors.initials: QS
authors.lastname: Huang
authors.affiliation: Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 YouyiXilu, Xi'an 710072, Shaanxi, PR China. Electronic address: yindc@nwpu.edu.cn.
authors.forename: Da-Chuan
authors.initials: DC
authors.lastname: Yin
authors.affiliation: Key Laboratory for Space Bioscience and Space Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 YouyiXilu, Xi'an 710072, Shaanxi, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Shang
mesh_terms: D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology* / Q000502:physiology*; D006899:Mixed Function Oxygenases / Q000494:pharmacology*; D055607:Receptors, Natural Killer Cell / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: D016207:Cytokines; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins; D006899:Mixed Function Oxygenases; C058291:aspartic acid 2-oxoglutarate-dependent dioxygenase
keywords: Cytotoxicity; Human aspartyl β-hydroxylase (HAAH); Human natural killer (NK) cells; Tumor immune surveillance