Cocaine interacts with macrophages to modulate mesangial cell proliferation

Area of Science:

• Nephrology
• Immunology
• Toxicology

Background:

• Human immunodeficiency virus (HIV) infection is linked to focal segmental glomerulosclerosis (FSGS).
• Cocaine abuse is common in HIV patients with renal disease, but its role in FSGS is unclear.
• Mesangial cell (MC) proliferation is a critical factor in glomerulosclerosis development.

Purpose of the Study:

• To investigate if cocaine directly or indirectly affects mesangial cell proliferation.
• To determine the role of macrophages (M phi) in cocaine's effect on MCs.
• To elucidate the involvement of cytokines like transforming growth factor-beta (TGF-β) and interleukin-6 (IL-6).

Main Methods:

• In vitro study using human mesangial cells and macrophages.
• Incubation of MCs with macrophage-conditioned media containing cocaine.
• Use of neutralizing antibodies against TGF-β and IL-6.
• Direct incubation of MCs with TGF-β and IL-6.

Main Results:

• Cocaine alone did not affect MC proliferation.
• Secretory products from cocaine-exposed macrophages significantly enhanced MC proliferation.
• The effect of cocaine was concentration-dependent.
• Neutralizing antibodies to IL-6 attenuated the proliferative effect, while antibodies to TGF-β augmented it.
• Direct IL-6 increased MC proliferation, while TGF-β suppressed it.

Conclusions:

• Cocaine modulates mesangial cell proliferation indirectly through macrophage interaction.
• Interleukin-6 and transforming growth factor-beta play significant roles in this cocaine-induced modulation.
• Cocaine may be a contributing factor to focal segmental glomerulosclerosis in HIV-infected individuals.