Galey D, Woodward J, Nath A; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 64 (abstract no. 70).
Univ of Kentucky, Lexington.
Background: Cytokines and chemokines have been implicated in a multifaceted way in neurological complications associated with human immunodeficiency virus type 1 (HIV-1). Given the large number of astrocytes in the CNS, we hypothesized that they may have a key role in the production of cytokines and chemokines. Therefore, we determined the regulatory affect of HIV and its proteins, Tat and gp120, on astrocytes. Methods: Human fetal astrocytes (1 <times> 10(6)) were cultured in DMEM + 10% FBS and treated with Tat (125 nM) and/or gp120 (250 pM) in serum-free DMEM for 6 hours at 37 degrees C. The cells were lysed and the RNA was extracted. Separate samples were infected with HIV(NL4-3). After 3 days, RNA was extracted and analyzed by a ribonuclease protection assay. Each experiment was performed in triplicate. Each result was analyzed in proportion to the L32 housekeeping gene. The ratios were analyzed by Student's t-test. Results: In general, chemokine and cytokine production occurred either by infection by HIV or by Tat treatment. gp120 induced the production of only MCP-1 (4x, p < 0.005). Chemokines IP-10, IL-8, and MCP-1, as well as the cytokine IL-6, were induced by either HIV infection or Tat treatment (4- 8x, p < 0.005). Increases in RANTES (7x, p < 0.005) and IL-8 (2x, p < 0.005) occurred with HIV infection alone, while only Tat treatment resulted in induction of IL-1 alpha (3x, p < 0.005) and beta (10x, p < 0.005). No significant effect of any of the treatments was noted in IL-12, IL-10, IL-1Ra, IFN-gamma, LTN, or I-309 induction. Conclusions: Chemokine and cytokine production by astrocytes is regulated by HIV infection or by its proteins, particularly Tat. The pattern of chemokine and cytokine production suggests that these cells may play an important role in pathogenesis of HIV dementia and CNS opportunistic infections by mediating infiltration of monocytes and lymphocytes. Some of these substances may also cause neuronal injury.
Publication Types:
Keywords:
- AIDS Dementia Complex
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Astrocytes
- CCL1 protein, human
- CXCL10 protein, human
- Chemokine CCL5
- Chemokines
- Chemokines, CC
- Chemokines, CXC
- Cytokines
- Gene Products, tat
- HIV Envelope Protein gp120
- HIV Infections
- HIV Seropositivity
- HIV-1
- Humans
- Interleukin-1
- Interleukin-6
- Interleukin-8
- immunology
Other ID:
UI: 102243850
From Meeting Abstracts