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.
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.
Kim
Byung Oh
BO
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Liu
Ying
Y
Zhou
Betty Y
BY
He
Johnny J
JJ
D020816:Amino Acid Motifs; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019744:Chemokines, C / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000737:chemistry; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D012795:Sialoglycoproteins / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus
D019744:Chemokines, C; D015696:Gene Products, tat; D008222:Lymphokines; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C092390:XCL1 protein, human; C486249:Xcl1 protein, mouse; C018997:lymphotactin; D054322:tat Gene Products, Human Immunodeficiency Virus