Inhibitory effects of human immunodeficiency virus gp120 and Tat on CpG-A-induced inflammatory cytokines in plasmacytoid dendritic cells

• Published in: Acta biochimica et biophysica Sinica Vol. 44; no. 9; pp. 797 - 804
• Main Authors: Fang, Meixin, Xu, Ning, Shao, Xueting, Yang, Jin, Wu, Nanping, Yao, Hangping
• Format: Journal Article
• Language: English
• Published: China 01.09.2012
• Subjects: Antigens, Surface - metabolism; Cells, Cultured; Chemokine CXCL10 - metabolism; Cytokines - metabolism; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp120 - pharmacology; Human immunodeficiency virus; Humans; Inflammation Mediators - metabolism; Interferon-alpha - metabolism; Interferon-beta - metabolism; Interleukin-6 - metabolism; Lectins, C-Type - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Membrane Glycoproteins - metabolism; Oligodeoxyribonucleotides - pharmacology; Receptors, Immunologic - metabolism; Recombinant Proteins - pharmacology; tat Gene Products, Human Immunodeficiency Virus - genetics; tat Gene Products, Human Immunodeficiency Virus - pharmacology; Tumor Necrosis Factor-alpha - metabolism; 人类免疫缺陷病毒; 包膜糖蛋白; 抑制作用; 树突状细胞; 浆细胞; 炎性细胞因子; 诱导蛋白; 酶联免疫吸附测定法
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gms062

Plasmacytoid dendritic cells （pDCs）, not only inhibit viral replication, but also play an essential role in linking the innate and adaptive immune system. In this study, we explored the effects of human immunodeficiency virus （HIV） gpl20 and tat on CpG-A-induced inflammatory cytokines in pDCs. The results provided fundamental insights into HIV pathogenesis that may hold promise for preventative and even curative strategies, pDCs were isolated using blood DC antigen 4 （BDCA-4） DC isolation kit, and the purity was analyzed using BDCA-2 anti- body by flow cytometry, pDCs and peripheral blood mononuclear cells （PBMCs） were stimulated by either CpG-A （5 μg/mi）, gpl20 （0.5 μg/ml）, tat （0.5 μg/ml）, or CpG-A treatment combined with gp120 or tat. The production of type I interferons （IFNs） and other inflammatory cytokines, including tumor necrosis factor-alpha （TNF-α, interlukine-6 （IL-6）, and interferon-gamma- inducible protein-10 （IP-10） in the culture supernatant,was determined by enzyme-linked immunosorbent assay. The results showed that CpG-A induced high levels of type I IFNs and other inflammatory cytokines, including TNF-α, IL-6, and IP-10, in pDCs. Concomitant treatment with gpl20 reduced the levels of IFN-α, IFN-β, TNF-α, IL-6, and IP-10 induced by CpG-A in pDCs by 79%, 53%, 60%, 50%, and 34%, respectively, while tat suppressed them by 88%, 66%, 71%, 64%, and 53%, respectively. Similar results were demonstrated in CpG- A-treated PBMCs. In conclusion, gpl20 and tat are effective inhibitors of the CpG-A-mediated induction of type I IFNs and other inflammatory cytokines from pDCs and PBMCs.