Abstract
HIV-1 infection and nicotine addiction are global public health crises. In the central nervous system, HIV-1 causes a devastating neurodegenerative disease. It is well recognized that microglial cells play a pivotal role in the neuropathogenesis of HIV-1 and that drugs of abuse not only contribute to the spread of this agent but may facilitate viral expression in these brain macrophages. Nicotine has been shown to stimulate the production of HIV-1 by in vitro-infected alveolar macrophages, and the HIV-1 protein gp120 binds to nicotinic receptors. In this study, we demonstrated the constitutive expression of nicotinic acetylcholine receptor mRNA in primary human microglial cells and showed that the pretreatment of microglia with nicotine increased HIV-1 expression in a concentration-dependent manner, as measured by p24 antigen levels in culture supernatants. We also found that nicotine robustly altered the gene expression profile of HIV-1-infected microglia and that the transforming growth factor-β1 is involved in the enhanced expression of HIV-1 by nicotine.
References
Abbud RA, Finegan CK, Guay LA, Rich EA (1995) Enhanced production of human immunodeficiency virus type 1 by in vitro-infected alveolar macrophages from otherwise healthy cigarette smokers. J Infect Dis 172:859–863
Bell JE (2004) An update on the neuropathology of HIV in the HAART era. Histopathology 45:549–559
Bracci L, Lozzi L, Rustici M, Neri P (1992) Binding of HIV-1 gp120 to the nicotinic receptor. FEBS Lett 311:115–118
Chong IW, Lin SR, Hwang JJ, Huang MS, Wang TH, Hung JY, Paulauskis JD (2002) Expression and regulation of the macrophage inflammatory protein-1 alpha gene by nicotine in rat alveolar macrophages. Eur Cytokine Netw 13:242–249
Gekker G, Hu S, Sheng WS, Rock RB, Lokensgard JR, Peterson PK (2006) Cocaine-induced HIV-1 expression in microglia involves sigma-1 receptors and transforming growth factor-beta1. Int Immunopharmacol 6:1029–1033
Ghosheh OA, Dwoskin LP, Miller DK, Crooks PA (2001) Accumulation of nicotine and its metabolites in rat brain after intermittent or continuous peripheral administration of [2′-(14)C]nicotine. Drug Metab Dispos 29:645–651
Giunta B, Ehrhart J, Townsend K, Sun N, Vendrame M, Shytle D, Tan J, Fernandez F (2004) Galantamine and nicotine have a synergistic effect on inhibition of microglial activation induced by HIV-1 gp120. Brain Res Bull 64:165–170
Ho WZ, Guo CJ, Yuan CS, Douglas SD, Moss J (2003) Methylnaltrexone antagonizes opioid-mediated enhancement of HIV infection of human blood mononuclear phagocytes. J Pharmacol Exp Ther 307:1158–1162
Nath A, Hauser KF, Wojna V, Booze RM, Maragos W, Prendergast M, Cass W, Turchan JT (2002) Molecular basis for interactions of HIV and drugs of abuse. J Acquir Immune Defic Syndr 31(Suppl 2):S62–S69
Nouri-Shirazi M, Guinet E (2003) Evidence for the immunosuppressive role of nicotine on human dendritic cell functions. Immunology 109:365–373
Peterson PK, Gekker G, Chao CC, Schut R, Molitor TW, Balfour HH Jr (1991) Cocaine potentiates HIV-1 replication in human peripheral blood mononuclear cell cocultures. Involvement of transforming growth factor-beta. J Immunol 146:81–84
Peterson PK, Gekker G, Hu S, Cabral G, Lokensgard JR (2004) Cannabinoids and morphine differentially affect HIV-1 expression in CD4(+) lymphocyte and microglial cell cultures. J Neuroimmunol 147:123–126
Roth MD, Whittaker KM, Choi R, Tashkin DP, Baldwin GC (2005) Cocaine and sigma-1 receptors modulate HIV infection, chemokine receptors, and the HPA axis in the huPBL-SCID model. J Leukoc Biol 78:1198–1203
Shytle RD, Mori T, Townsend K, Vendrame M, Sun N, Zeng J, Ehrhart J, Silver AA, Sanberg PR, Tan J (2004) Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors. J Neurochem 89:337–343
Sopori ML, Kozak W (1998) Immunomodulatory effects of cigarette smoke. J Neuroimmunol 83:148–156
Sugano N, Shimada K, Ito K, Murai S (1998) Nicotine inhibits the production of inflammatory mediators in U937 cells through modulation of nuclear factor-kappaB activation. Biochem Biophys Res Commun 252:25–28
Suzuki T, Hide I, Matsubara A, Hama C, Harada K, Miyano K, Andra M, Matsubayashi H, Sakai N, Kohsaka S, Inoue K, Nakata Y (2006) Microglial alpha7 nicotinic acetylcholine receptors drive a phospholipase C/IP3 pathway and modulate the cell activation toward a neuroprotective role. J Neurosci Res 83:1461–1470
Tomlinson GS, Simmonds P, Busuttil A, Chiswick A, Bell JE (1999) Upregulation of microglia in drug users with and without pre-symptomatic HIV infection. Neuropathol Appl Neurobiol 25:369–379
Totti N 3rd, McCusker KT, Campbell EJ, Griffin GL, Senior RM (1984) Nicotine is chemotactic for neutrophils and enhances neutrophil responsiveness to chemotactic peptides. Science 223:169–171
Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421:384–388
Acknowledgments
This work was supported by grants from National Institute on Drug Abuse, DA-020398, and was also supported in part by the U.S. Public Health Service grant DA020398.
Author information
Authors and Affiliations
Corresponding author
Additional information
Human fetal brain tissue was obtained under the protocol approved by the Human Subjects Research Committee at our institution.
None of the authors has a commercial or other association that might pose a conflict of interest with the current study.
Rights and permissions
About this article
Cite this article
Rock, R.B., Gekker, G., Aravalli, R.N. et al. Potentiation of HIV-1 Expression in Microglial Cells by Nicotine: Involvement of Transforming Growth Factor-β1. J Neuroimmune Pharmacol 3, 143–149 (2008). https://doi.org/10.1007/s11481-007-9098-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11481-007-9098-7