HIV-1 kills renal tubular epithelial cells in vitro by triggering an apoptotic pathway involving caspase activation and Fas upregulation.

Conaldi, Pier Giulio; Biancone, Luigi; Bottelli, Antonella; Wade-Evans, A.M.; Racusen, Lorraine C.; Boccellino, Mariarosaria; Orlandi, Viviana Teresa; Serra, Caterina; Camussi, Giovanni; Toniolo, Antonio

doi:10.1172/jci3480

Cited by 148 publications

(121 citation statements)

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“…SB202190 and the rabbit anti-fibronectin antibody were from Calbiochem (Nottingham, UK). The protein kinase C (PKC) peptide inhibitors PKC [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and SN50 were from Alexis (Nottingham, UK) and the TransAM nuclear factor kappa B (NF-κB) kit was from Active Motif (Rixensart, Belgium). The FITC-conjugated rabbit antimouse antibody, the rabbit anti-fibronectin antibody and the avidin/biotin blocking solution were from DAKOCytomation (Glostrup, Denmark).…”

Section: Methodsmentioning

confidence: 99%

“…Tissue was analysed by light microscopy and by immunofluorescence to confirm the absence of tumour cells and to exclude the presence of glomerular abnormalities. Differentiated immortalised HMCs were obtained by infection of a pure primary culture with a hybrid Adeno5/SV40 virus [19]. Individual foci of immortalised cells were subcultured and characterised according to phenotype.…”

Section: In Vitro Studymentioning

confidence: 99%

“…Inhibition experiments on basal protein production were carried out simultaneously. RS102895 (6 μmol/l), anti-TGF-β1 neutralising antibody (2 μg/ml), SN50 (18 μmol/l), SB202190 (1 μmol/l) and PKC [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] (4 μmol/l) were used to block CCR2, TGF-β1, NF-κB, p38 mitogen-activated protein (MAP) kinase and PKC, respectively. The specificity and selectivity of the inhibitors used has been previously demonstrated [22][23][24][25].…”

Section: In Vitro Studymentioning

confidence: 99%

“…Results are expressed as fold increase over control. n=3; *p<0.05 for MCP-1, MCP-1 + PKC [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and MCP-1 + SB202190 vs control. b Serum-deprived HMCs were exposed to rh-MCP-1 (10 ng/ ml) for 0, 30, 60 and 120 min.…”

Section: Mcp-1 Deficiency Attenuates Glomerular Fibronectin Depositiomentioning

confidence: 99%

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Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells

et al. 2007

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Aims/hypothesis Diabetic nephropathy is characterised by mesangial extracellular matrix accumulation. Monocyte chemoattractant protein-1 (MCP-1), a chemokine promoting monocyte infiltration, is upregulated in the diabetic glomerulus. We performed in vitro and in vivo studies to examine whether MCP-1 may have prosclerotic actions in the setting of diabetes, presumably via its receptor, chemokine (C-C motif) receptor 2 (CCR2), which has been described in mesangial cells. Methods Human mesangial cells were exposed to recombinant human (rh)-MCP-1 (100 ng/ml) for 12, 24 and 48 h and to rh-MCP-1 (10, 100 and 200 ng/ml) for 24 h. Fibronectin, collagen IV and transforming growth factor, beta 1 (TGF-β1) protein levels were measured by ELISA and pericellular polymeric fibronectin levels by western blotting. The intracellular mechanisms were investigated using specific inhibitors for CCR2, nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase and protein kinase C, and an anti-TGF-β1 blocking antibody. In both non-diabetic and streptozotocin-induced diabetic mice that were deficient or not in MCP-1, glomerular fibronectin accumulation was examined by immunohistochemistry, while cortical Tgf-β1 (also known as Tgfb1) and fibronectin mRNA and protein levels were examined by real-time PCR and western blotting. Results In mesangial cells, MCP-1 binding to CCR2 induced a 2.5-fold increase in fibronectin protein levels at 24 h followed by a rise in pericellular fibronectin, whereas no changes were seen in collagen IV production. MCP-1-induced fibronectin production was TGF-β1-and NF-κB-dependent. In diabetic mice, loss of MCP-1 diminished glomerular fibronectin protein production and both renal cortical Tgf-β1 and fibronectin mRNA and protein levels. Conclusions/interpretation Our in vitro and in vivo findings indicate a role for the MCP-1/CCR2 system in fibronectin deposition in the diabetic glomerulus, providing a new therapeutic target for diabetic nephropathy.

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Section: Methodsmentioning

confidence: 99%

Section: In Vitro Studymentioning

confidence: 99%

Section: In Vitro Studymentioning

confidence: 99%

Section: Mcp-1 Deficiency Attenuates Glomerular Fibronectin Depositiomentioning

confidence: 99%

See 2 more Smart Citations

Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells

et al. 2007

View full text Add to dashboard Cite

show abstract

“…[1][2][3][4][5] The latter is characterized by focal glomerulosclerosis and tubulointerstitial lesions. [6] Acute renal failure has frequently been reported as a result of tubular cell injury (apoptosis and necrosis) in HIV-1-infected patients.…”

Section: Introductionmentioning

confidence: 99%