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HIV enhances substance P expression in human immune cells
Wen-Zhe Ho1, Jian-Ping Lai, Yuan Li
1The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Summary
Human immune cells produce Substance P (SP), a key regulator of neuroimmunoregulation. HIV infection increases SP levels, with immune cells like macrophages and lymphocytes being the primary source, linked to viral replication.
Area of Science:
- Immunology
- Neuroscience
- Virology
Background:
- Substance P (SP) modulates neuroimmunoregulation and is present in human immune cells.
- Elevated plasma SP levels are observed in HIV-infected individuals.
Purpose of the Study:
- To identify the cellular source of increased SP levels in HIV infection.
- To investigate the mechanisms by which HIV influences SP expression in immune cells.
Main Methods:
- Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify SP mRNA expression.
- Culturing of monocyte-derived macrophages (MDM) and lymphocytes.
- Treatment of MDM with recombinant HIV envelope glycoprotein 120 (gp120) and soluble CD4.
- Activation of latently HIV-infected cell lines (U1 and ACH-2).
Main Results:
- MDM and lymphocytes express SP mRNA, with significantly increased levels in HIV infection.
- HIV-induced SP expression in MDM correlates positively with viral replication.
- HIV gp120 enhances SP mRNA expression in MDM, an effect blocked by soluble CD4.
- HIV activation up-regulates SP mRNA in latently infected cell lines.
Conclusions:
- HIV infection increases SP expression in human immune cells, particularly macrophages and lymphocytes.
- HIV gp120 and viral replication are key drivers of enhanced SP production.
- The interaction between HIV and SP is relevant to the immunopathogenesis of HIV infection and AIDS.