Mechanism of HIV-1-TAT induction of interleukin-1beta from human monocytes: Involvement of the phospholipase C/protein kinase C signaling cascade

• Published in: Journal of medical virology Vol. 82; no. 5; pp. 735 - 746
• Main Authors: Yang, Yongbo, Wu, Jianguo, Lu, Yuanan
• Format: Journal Article
• Language: English
• Published: United States 01.05.2010
• Subjects: HIV-1 - immunology; Humans; Interleukin-1beta - biosynthesis; Monocytes - immunology; Protein Kinase C - metabolism; Signal Transduction; tat Gene Products, Human Immunodeficiency Virus - immunology; Type C Phospholipases - metabolism
• ISSN: 1096-9071
• DOI: 10.1002/jmv.21720

Human immunodeficiency virus TAT plays an important role in the disregulation of cytokine production associated with the neurological disorders that follow HIV infection. IL-1beta is one of the important inflammatory cytokines secreted by immune-activated monocytes/macrophages. Previous reports have shown that extracellular TAT stimulates IL-1beta expression in monocytes/macrophages. However, little is known about the mechanisms and possible TAT-responsive elements within the IL-1beta promoter. The present study shows that TAT increases the production of IL-1beta in human monocytes; PLC-PKC pathway-dependent phosphorylation of p44/42 and JNK MAP kinases participates partially in IL-1beta induction by TAT; specific C/EBP and NF-kappaB transcription factor binding elements within the IL-1beta promoter are involved in TAT regulation of IL-1beta production. This study identifies a signaling mechanism for HIV-1-induced IL-1beta production in human monocytes that may be involved in the neuropathogenesis of HIV-associated dementia.