title: Viral IL-10 down-regulates the "MHC-I antigen processing operon" through the NF-κB signaling pathway in nasopharyngeal carcinoma cells.
abstract: The HLA-I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The loss of surface expression of HLA-I molecules is particularly important as this enables tumor cells to evade recognition and lysis by cytotoxic T-lymphocytes. Transcriptional control of the APM genes is regulated by the nuclear factor kappa B (NF-κB). BCRFl is an Epstein-Barr virus homologue of human IL-10 (hIL-10) and is known as viral IL-10 (vIL-10). vIL-10 shares many immunosuppressive effects with hIL-10 but lacks the immunostimulatory effect of hIL-10. The aim of this study was to assess whether vIL-10 inhibits APM components (TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I) through the NF-κB signaling pathway in nasopharyngeal carcinoma. This work demonstrated that vIL-10 inhibited NF-κB activation by blocking IKK phosphorylation and promoting the expression of IKB. TNF-α treatment led to a strong translocation of NF-κB p65, whereas pretreatment with vIL-10 before TNF-α treatment blocked NF-κB p65 translocation. vIL-10 also inhibited TNF-α-induced DNA-binding of NF-κB p65 in the nucleus. Furthermore, chromatin immunoprecipitation analysis demonstrated that NF-κB p65 could bind to the TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I gene promoters, and after TNF-α stimulation, the down-regulation of TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I transcription by vIL-10 correlated with the suppression of NF-κB in CNE-2 cells. Surprisingly, vIL-10 inhibits only TAP-1 and LMP-7 transcription in CNE-1 cells. Taken together, these results suggest that the inhibition of NF-κB activity may be an important mechanism for vIL-10 suppression of APM (TAP-1, TAP-2, LMP-2, LMP-7 and HLA-I) gene transcription in CNE-2 cells.
authors.affiliation: Head and Neck Tumor Research Center, Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Yan-Xin
authors.initials: YX
authors.lastname: Ren
authors.affiliation: Head and Neck Tumor Research Center, Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Head and Neck Tumor Research Center, Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Rui-Mei
authors.initials: RM
authors.lastname: Sun
authors.affiliation: Department of Pathology, Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Head and Neck Tumor Research Center, Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Liu-Fang
authors.initials: LF
authors.lastname: Zhao
authors.affiliation: Head and Neck Tumor Research Center, Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Bao-Zhong
authors.initials: BZ
authors.lastname: Li
authors.affiliation: Head and Neck Tumor Research Center, Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, 650118, Yunnan, China.
authors.forename: Hai-Ting
authors.initials: HT
authors.lastname: Long
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, 650118, Yunnan, China.
authors.forename: Qiang-Ming
authors.initials: QM
authors.lastname: Sun
authors.affiliation: Department of Cardiothoracic Surgery, Third Affiliated Hospital of Kunming Medical University, Kunming, China.
authors.forename: Yun-Chao
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Head and Neck Tumor Research Center, Third Affiliated Hospital of Kunming Medical University, Kunming, China. lixiaojiang1@hotmail.com.
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Li
keywords: Antigen presentation; Nasopharyngeal neoplasms; Nuclear factor Kappa B (NF-κB); Viral interleukin-10 (vIL-10)