HIV-1 Tat and gp120 Regulate Astrocyte Tissue Inhibitor of Matrix Metalloproteinases-1 (TIMP)-1
dc.creator | Joshi, Chaitanya R. | |
dc.creator | Ghorpade, Anuja | |
dc.date.accessioned | 2019-08-22T19:39:18Z | |
dc.date.available | 2019-08-22T19:39:18Z | |
dc.date.issued | 2015-03 | |
dc.date.submitted | 2015-03-05T15:22:03-08:00 | |
dc.description | Research Appreciation Day Award Winner - 2015 Department of Cell Biology and Immunology - 1st Place Poster Award | |
dc.description | Research Appreciation Day Award Winner - 2015 Robert J. Wordinger Excellence in Virology Research Poster Presentation - 2nd Place Award | |
dc.description.abstract | Purpose: While antiretroviral therapy (ART) has improved the quality of life and survival of HIV-1-infected patients, HIV-1-associated neurocognitive disorders (HAND) remain a major problem in over 30% of cases. All forms of HAND are associated with CNS inflammation. Astrocytes, the principal type of glial cells, are involved in signaling, homeostasis, and repair during CNS pathology. Some astrocytes become non-productively infected by HIV-1. The balance between matrix metalloproteinases (MMP) and their inhibitors must be tightly regulated during CNS inflammation. In the brain, tissue inhibitor of MMPs (TIMP)-1 protects human neurons from HIV-1-induced apoptosis and is mainly produced by astrocytes. Further, astrocyte TIMP-1 is differentially regulated during acute and chronic IL-1β-activation. However, the direct or indirect effects of astrocyte HIV-1 protein expression on TIMP-1 regulation are not well studied. Here, we investigated downstream effects of HIV-1 Tat and gp120 expression in astrocytes on the TIMP-1/MMP balance. Methods: Primary human astrocytes were transfected with HIV-1 protein-expressing plasmids (Tat72, Tat101, gp120JR-FL). First, HIV-1 Tatand gp120 expression levels were compared using RT2-PCR and western blot. Cell viability and proliferation were evaluated as measures of cytotoxicity using MTT and BrdU assays, respectively. Concurrently, time-dependent changes in TIMP-1 and CCL2 mRNA and protein levels were measured as indicators of astrocyte activation. Since C/EBPβ is a known TIMP-1 regulator, alterations in C/EBPβ mRNA and protein levels were analyzed. Results: HIV-1 Tat and gp120 expression in astrocytes significantly reduced cell viability. Transfected astrocytes showed higher cytokine and chemokine mRNA as well as protein levels. C/EBPβ mRNA expression was differentially altered in astrocytes expressing either HIV-1 Tat72, Tat101 and gp120 indicating potentially distinct underlying mechanisms. Conclusions: We propose that TIMP-1 is differentially regulated by HIV-1 protein expression in astrocytes, which mimic viral CNS reservoirs, and may have implications in HAND neuropathogenesis. | |
dc.identifier.uri | https://hdl.handle.net/20.500.12503/26594 | |
dc.language.iso | en | |
dc.title | HIV-1 Tat and gp120 Regulate Astrocyte Tissue Inhibitor of Matrix Metalloproteinases-1 (TIMP)-1 | |
dc.type | poster | |
dc.type.material | text |