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Signalling pathways...
Signalling pathways regulating inducible nitric oxide synthase expression in human kidney epithelial cells
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- Poljakovic, Mirjana (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden
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- Nygren, Jens Martin, 1976- (författare)
- Lund University,Lunds universitet,Medicinska fakulteten,Faculty of Medicine,Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden
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- Persson, Katarina (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine,Department of Clinical Pharmacology, Lund University Hospital, SE-221 85, Lund, Sweden
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(creator_code:org_t)
- 2003
- 2003
- Engelska.
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Ingår i: European Journal of Pharmacology. - 0014-2999 .- 1879-0712. ; 469:1-3, s. 21-28
- Relaterad länk:
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Abstract
Ämnesord
Stäng
- The purpose of this study was to elucidate the signalling pathways involved in the cytokine-activated inducible nitric oxide synthase (iNOS) response in a human kidney epithelial cell line, A498. Unstimulated cells did not express iNOS. Exposure of A498 cells to a cytokine mixture consisting of interferon gamma, interleukin-1 beta and tumor necrosis factor-alpha (TNF-alpha) increased nitrite production, iNOS mRNA and protein expression. Pharmacological inhibition of tyrosine kinases, including janus kinase (JAK2), and protein kinase C (PKC) inhibited cytokine-mediated nitrite production and iNOS protein expression. The involvement of mitogen-activated protein kinases (MAPKs) was investigated. Inhibition of p38 MAPK, but not of an upstream activator of extracellular signal-regulated kinase (ERK), caused a decrease in iNOS expression and nitrite production in response to cytokines. Electrophoretic mobility shift assay of nuclear extract from cytokine-stimulated cells demonstrated a pronounced binding to a nuclear factor kappa B (NF-kappa B) sequence present in the human iNOS promoter. Furthermore, the NF-kappa B inhibitor pyrrolidinedithiocarbamate (PDTC) decreased cytokine-activated iNOS protein expression and nitrite production. The present study has demonstrated that cytokine-stimulated iNOS expression in human kidney epithelial cells involves activation of tyrosine kinases, including JAK2, PKC, p38 MAPK and NF-kappa B.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- MAP (mitogen-activated protein) kinase
- NF-κB (nuclear factor-κB)
- Nitric oxide (NO)
- Tyrosine kinase
- Urinary tract infection
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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