Induction of C Chemokine XCL1 (Lymphotactin/Single C Motif-1{alpha}/Activation-Induced, T Cell-Derived and Chemokine-Related Cytokine) Expression by HIV-1 Tat Protein

• Published in: The Journal of immunology (1950) 2004-02, Vol.172 (3), p.1888-1895
• Main Authors: Kim, Byung Oh, Liu, Ying, Zhou, Betty Y, He, Johnny J
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Animals; Astrocytes - immunology; Astrocytes - metabolism; Brain - cytology; Brain - immunology; Brain - metabolism; Brain - virology; Cell Line, Tumor; Cells, Cultured; Chemokines, C - biosynthesis; Chemokines, C - chemistry; Chemokines, C - genetics; Gene Expression Regulation; Gene Products, tat - biosynthesis; Gene Products, tat - genetics; Gene Products, tat - physiology; HIV-1 - genetics; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; Lymphocyte Activation; Lymphokines - chemistry; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Transgenic; Microglia - immunology; Microglia - metabolism; Monocytes - immunology; Monocytes - metabolism; Promoter Regions, Genetic; RNA, Messenger - biosynthesis; Sialoglycoproteins - chemistry; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; tat Gene Products, Human Immunodeficiency Virus; Tat protein; Up-Regulation - genetics; XCL1 protein
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.3.1888

HIV-1 Tat has been proposed as a key agent in many AIDS-related disorders, including HIV-1-associated neurological diseases. We have recently shown that Tat expression induces a significant increase in T lymphocytes in the brains of Tat transgenic mice. The CNS infiltration of T lymphocytes has been noted in AIDS patients. In the present study using this unique genetic system we attempted to understand the underlying mechanisms of Tat expression-induced infiltration of T lymphocytes by examining chemokine expression. RNase protection assay revealed that in addition to CCL2 (monocyte chemoattractant protein-1), CCL3 (macrophage inflammatory protein-1alpha (MIP-1alpha)), CCL4 (MIP-1beta), CCL5 (RANTES), CXCL2 (MIP-2), and CXCL10 (inducing protein-10), XCL1 (lymphotactin/single C motif-1alpha/activation-induced, T cell-derived and chemokine-related cytokine) was identified to be up-regulated by Tat expression. XCL1 is a C chemokine and plays a specific and important role in tissue-specific recruitment of T lymphocytes. Thus, we further determined the relationship between Tat and XCL1 expression. Tat-induced XCL1 expression was further confirmed by XCL1-specific RT-PCR and ELISA. Combined in situ hybridization and immunohistochemical staining identified astrocytes, monocytes, and macrophages/microglia as XCL1-producing cells in vivo. Using human astrocytes, U87.MG cells, as an in vitro model, activation of XCL1 expression was positively correlated with Tat expression. Moreover, the XCL1 promoter-driven reporter gene assay showed that Tat-induced XCL1 expression occurred at the transcriptional level. Taken together, these results demonstrate that Tat directly trans-activated XCL1 expression and suggest potential roles of Tat-induced XCL1 expression in the CNS infiltration of T lymphocytes during HIV-1 infection and subsequent HIV-1-induced neurological diseases.