Renal cell cytokine production stimulates HIV-1 expression in chronically HIV-1-infected monocytes.
Renal infiltration of human immunodeficiency virus type 1 (HIV-1)-infected monocytes might play an important role in the development of HIV-associated nephropathy (HIVAN). In the present study, we investigated the effects of cytokines produced by cultured human mesangial cells (HMC) and proximal tubular epithelial cells (PTEC) on HIV-1 expression in chronically HIV-1-infected promonocytes (U1 cells). Human mesangial cells constitutively secreted interleukin-6 (IL-6) but not tumor necrosis factor-alpha (TNF-alpha) into the culture medium, whereas PTEC constitutively secreted both IL-6 and TNF-alpha. Coculture of U1 cells with HMC or PTEC for 72 hours markedly stimulated HIV-1 expression, with the p24 antigen concentration in the coculture supernatants ranging from approximately 200 to 1850 pg/ml. The presence of anti-IL-6 antibody in the coculture medium nearly completely blocked HIV-1 expression in the HMC/U1 cell cocultures (P < 0.05). Anti-IL-6 antibody and anti-TNF-alpha antibody blocked HIV-1 expression in the PTEC/U1 cell cocultures by 40% and 53%, respectively (P < 0.05). Moreover, the combination of anti-IL-6 and anti-TNF-alpha antibodies additively reduced coculture HIV-1 expression by 87% (P < 0.05). We conclude that renal cell production of IL-6 and TNF-alpha might provide a potent stimulus for HIV-1 expression in HIV-1-infected monocytes that infiltrate the kidney, and that this may play an important role in the pathogenesis of HIVAN.
O'Donnell
M P
MP
Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota, USA.
Chao
C C
CC
Gekker
G
G
Modi
K S
KS
Kasiske
B L
BL
Keane
W F
WF
D016263:AIDS-Associated Nephropathy / Q000209:etiology* / Q000821:virology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology; D005920:Glomerular Mesangium / Q000166:cytology / Q000276:immunology; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D007668:Kidney / Q000166:cytology / Q000276:immunology* / Q000821:virology; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000276:immunology; D009000:Monocytes / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014779:Virus Replication
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha