Abstract
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.