Protein overload induces fractalkine upregulation in proximal tubular cells through nuclear factor κB- and p38 mitogen-activated protein kinase-dependent pathways

Roberta Donadelli, Cristina Zanchi, Marina Morigi, Simona Buelli, Cristian Batani, Susanna Tomasoni, Daniela Corna, Daniela Rottoli, Ariela Benigni, Mauro Abbate, Giuseppe Remuzzi, Carla Zoja

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Abstract

Investigated was the effect of high albumin concentrations on proximal tubular cell expression of fractalkine. Human proximal tubular cells (HK-2) were incubated with human serum albumin (HSA), which induced a dose-dependent increase in fractalkine mRNA associated with increased levels of both membrane-bound and soluble forms of the protein. To evaluate the role of nuclear factor κB (NF-κB) activation in HSA-induced fractalkine mRNA, HK-2 cells were infected with a recombinant adenovirus encoding the natural inhibitor of NF-κB, IkBα; a 43% reduction of fractalkine mRNA levels resulted. Similarly, when cells were infected with the recombinant adenovirus expressing dominant negative mutant of the IkB kinase 2, a 55% inhibition of fractalkine mRNA was achieved. p38 mitogen-activated protein kinase was activated by HSA and was involved in NF-κB-dependent transcription of fractalkine. In kidneys of mice with bovine serum albumin overload proteinuria, fractalkine mRNA levels were 2.3-fold greater than those of controls. Fractalkine expression was also induced in tubular epithelial cells in this model. Anti-CXCR1 antibody treatment limited interstitial accumulation of mononuclear cells. Protein overload is a promoter of fractalkine gene induction mediated by NF-κB and p38 activation in proximal tubular cells. Fractalkine might contribute to direct mononuclear cells into peritubular interstitium and enhance their adhesion property, which in turn would favor inflammation and disease progression.

Original languageEnglish
Pages (from-to)2436-2446
Number of pages11
JournalJournal of the American Society of Nephrology
Volume14
Issue number10
DOIs
Publication statusPublished - Oct 1 2003

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Chemokine CX3CL1
p38 Mitogen-Activated Protein Kinases
Up-Regulation
Proteins
Messenger RNA
Serum Albumin
Adenoviridae
Bovine Serum Albumin
Proteinuria
Disease Progression
Anti-Idiotypic Antibodies
Albumins
Phosphotransferases
Epithelial Cells

ASJC Scopus subject areas

  • Nephrology

Cite this

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title = "Protein overload induces fractalkine upregulation in proximal tubular cells through nuclear factor κB- and p38 mitogen-activated protein kinase-dependent pathways",
abstract = "Investigated was the effect of high albumin concentrations on proximal tubular cell expression of fractalkine. Human proximal tubular cells (HK-2) were incubated with human serum albumin (HSA), which induced a dose-dependent increase in fractalkine mRNA associated with increased levels of both membrane-bound and soluble forms of the protein. To evaluate the role of nuclear factor κB (NF-κB) activation in HSA-induced fractalkine mRNA, HK-2 cells were infected with a recombinant adenovirus encoding the natural inhibitor of NF-κB, IkBα; a 43{\%} reduction of fractalkine mRNA levels resulted. Similarly, when cells were infected with the recombinant adenovirus expressing dominant negative mutant of the IkB kinase 2, a 55{\%} inhibition of fractalkine mRNA was achieved. p38 mitogen-activated protein kinase was activated by HSA and was involved in NF-κB-dependent transcription of fractalkine. In kidneys of mice with bovine serum albumin overload proteinuria, fractalkine mRNA levels were 2.3-fold greater than those of controls. Fractalkine expression was also induced in tubular epithelial cells in this model. Anti-CXCR1 antibody treatment limited interstitial accumulation of mononuclear cells. Protein overload is a promoter of fractalkine gene induction mediated by NF-κB and p38 activation in proximal tubular cells. Fractalkine might contribute to direct mononuclear cells into peritubular interstitium and enhance their adhesion property, which in turn would favor inflammation and disease progression.",
author = "Roberta Donadelli and Cristina Zanchi and Marina Morigi and Simona Buelli and Cristian Batani and Susanna Tomasoni and Daniela Corna and Daniela Rottoli and Ariela Benigni and Mauro Abbate and Giuseppe Remuzzi and Carla Zoja",
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T1 - Protein overload induces fractalkine upregulation in proximal tubular cells through nuclear factor κB- and p38 mitogen-activated protein kinase-dependent pathways

AU - Donadelli, Roberta

AU - Zanchi, Cristina

AU - Morigi, Marina

AU - Buelli, Simona

AU - Batani, Cristian

AU - Tomasoni, Susanna

AU - Corna, Daniela

AU - Rottoli, Daniela

AU - Benigni, Ariela

AU - Abbate, Mauro

AU - Remuzzi, Giuseppe

AU - Zoja, Carla

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N2 - Investigated was the effect of high albumin concentrations on proximal tubular cell expression of fractalkine. Human proximal tubular cells (HK-2) were incubated with human serum albumin (HSA), which induced a dose-dependent increase in fractalkine mRNA associated with increased levels of both membrane-bound and soluble forms of the protein. To evaluate the role of nuclear factor κB (NF-κB) activation in HSA-induced fractalkine mRNA, HK-2 cells were infected with a recombinant adenovirus encoding the natural inhibitor of NF-κB, IkBα; a 43% reduction of fractalkine mRNA levels resulted. Similarly, when cells were infected with the recombinant adenovirus expressing dominant negative mutant of the IkB kinase 2, a 55% inhibition of fractalkine mRNA was achieved. p38 mitogen-activated protein kinase was activated by HSA and was involved in NF-κB-dependent transcription of fractalkine. In kidneys of mice with bovine serum albumin overload proteinuria, fractalkine mRNA levels were 2.3-fold greater than those of controls. Fractalkine expression was also induced in tubular epithelial cells in this model. Anti-CXCR1 antibody treatment limited interstitial accumulation of mononuclear cells. Protein overload is a promoter of fractalkine gene induction mediated by NF-κB and p38 activation in proximal tubular cells. Fractalkine might contribute to direct mononuclear cells into peritubular interstitium and enhance their adhesion property, which in turn would favor inflammation and disease progression.

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