FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2020698032> ?p ?o ?g. }

• W2020698032 endingPage "106" @default.
• W2020698032 startingPage "96" @default.
• W2020698032 abstract "Extracellular signal-regulated kinase inhibition by statins inhibits neutrophil activation by ANCA.Background3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may modulate cellular inflammatory functions independent of serum cholesterol. We tested the hypothesis that statins decrease respiratory burst activity of human polymorphonuclear neutrophils (PMN) in response to anti-neutrophil cytoplasmic antibodies (ANCA).MethodsNeutrophils were isolated from healthy human volunteers, human immunoglobulins were isolated from patients with proteinase-3 (PR3)- and myeloperoxidase (MPO)-ANCA. Superoxide generation was measured by the ferricytochrome C assay and the nitro blue tetrazolium (NBT) test. ANCA antigen expression was measured by flow cytometry and phosphorylation of mitogen-activated protein kinase (MAPK) was assessed by Western blotting.ResultsCerivastatin and simvastatin inhibited respiratory burst activity to ANCA dose-dependently (1 to 25 μmol/L). Tumor necrosis factor-α (TNF-α)-primed neutrophils released 26.7 ± 2.8 nmol O2-/0.75 × 106 PMN/45 min and 10 μmol/L simvastatin reduced this amount to 18.0 ± 2.1 nmol. The inhibitory effect was confirmed by the NBT test. The respiratory burst decrease could not be reversed by 500 μmol/L mevalonic acid (MVA). In this assay, both statins also inhibited the response to human ANCA. PR3-ANCA resulted in 19.4 ± 2.0 nmol O2- nmol. This amount was decreased to 6.0 ± 1.2 nmol by preincubation with 10 μmol/L simvastatin (P < 0.01). For MPO-ANCA, the values were 22.6 ± 2.8 nmol for controls versus 16.7 ± 3.1 nmol with statin (P < 0.01). By FACS, simvastatin decreased TNF-α–mediated ANCA antigen translocation (from 219 ± 33 to 180 ± 35 MFI for PR3 and 24.0 ± 2.4 to 18.3 ± 1.1 for MPO). Finally, since p38 MAPK and ERK control TNF-α priming, we studied the effects of both statins on MAPK. Western blotting showed that statins inhibited TNF-α–induced ERK phosphorylation in a dose dependent fashion, but had no effect on p38.ConclusionThese findings demonstrate that HMG-CoA reductase inhibitors decrease respiratory burst activity of human PMN in response to ANCA. This effect was independent of mevalonate, but involved inhibition of ERK activation during TNF-α priming. Our data suggest that HMG-CoA reductase inhibitors may help limit inflammatory responses. Extracellular signal-regulated kinase inhibition by statins inhibits neutrophil activation by ANCA. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may modulate cellular inflammatory functions independent of serum cholesterol. We tested the hypothesis that statins decrease respiratory burst activity of human polymorphonuclear neutrophils (PMN) in response to anti-neutrophil cytoplasmic antibodies (ANCA). Neutrophils were isolated from healthy human volunteers, human immunoglobulins were isolated from patients with proteinase-3 (PR3)- and myeloperoxidase (MPO)-ANCA. Superoxide generation was measured by the ferricytochrome C assay and the nitro blue tetrazolium (NBT) test. ANCA antigen expression was measured by flow cytometry and phosphorylation of mitogen-activated protein kinase (MAPK) was assessed by Western blotting. Cerivastatin and simvastatin inhibited respiratory burst activity to ANCA dose-dependently (1 to 25 μmol/L). Tumor necrosis factor-α (TNF-α)-primed neutrophils released 26.7 ± 2.8 nmol O2-/0.75 × 106 PMN/45 min and 10 μmol/L simvastatin reduced this amount to 18.0 ± 2.1 nmol. The inhibitory effect was confirmed by the NBT test. The respiratory burst decrease could not be reversed by 500 μmol/L mevalonic acid (MVA). In this assay, both statins also inhibited the response to human ANCA. PR3-ANCA resulted in 19.4 ± 2.0 nmol O2- nmol. This amount was decreased to 6.0 ± 1.2 nmol by preincubation with 10 μmol/L simvastatin (P < 0.01). For MPO-ANCA, the values were 22.6 ± 2.8 nmol for controls versus 16.7 ± 3.1 nmol with statin (P < 0.01). By FACS, simvastatin decreased TNF-α–mediated ANCA antigen translocation (from 219 ± 33 to 180 ± 35 MFI for PR3 and 24.0 ± 2.4 to 18.3 ± 1.1 for MPO). Finally, since p38 MAPK and ERK control TNF-α priming, we studied the effects of both statins on MAPK. Western blotting showed that statins inhibited TNF-α–induced ERK phosphorylation in a dose dependent fashion, but had no effect on p38. These findings demonstrate that HMG-CoA reductase inhibitors decrease respiratory burst activity of human PMN in response to ANCA. This effect was independent of mevalonate, but involved inhibition of ERK activation during TNF-α priming. Our data suggest that HMG-CoA reductase inhibitors may help limit inflammatory responses." @default.
• W2020698032 created "2016-06-24" @default.
• W2020698032 creator A5017265102 @default.
• W2020698032 creator A5028287367 @default.
• W2020698032 creator A5049295400 @default.
• W2020698032 creator A5062825190 @default.
• W2020698032 creator A5079089312 @default.
• W2020698032 creator A5081283954 @default.
• W2020698032 date "2003-01-01" @default.
• W2020698032 modified "2023-09-27" @default.
• W2020698032 title "Extracellular signal-regulated kinase inhibition by statins inhibits neutrophil activation by ANCA" @default.
• W2020698032 cites W1606937999 @default.
• W2020698032 cites W1914154778 @default.
• W2020698032 cites W1965418020 @default.
• W2020698032 cites W1966797205 @default.
• W2020698032 cites W1994755070 @default.
• W2020698032 cites W2003307830 @default.
• W2020698032 cites W2006256574 @default.
• W2020698032 cites W2036498909 @default.
• W2020698032 cites W2039414389 @default.
• W2020698032 cites W2041565487 @default.
• W2020698032 cites W2043442756 @default.
• W2020698032 cites W2049872761 @default.
• W2020698032 cites W2050466097 @default.
• W2020698032 cites W2053794895 @default.
• W2020698032 cites W2054669785 @default.
• W2020698032 cites W2055285311 @default.
• W2020698032 cites W2065331193 @default.
• W2020698032 cites W2071986338 @default.
• W2020698032 cites W2074387820 @default.
• W2020698032 cites W2107254198 @default.
• W2020698032 cites W2108203235 @default.
• W2020698032 cites W2112933329 @default.
• W2020698032 cites W2113771464 @default.
• W2020698032 cites W2127708948 @default.
• W2020698032 cites W2129750583 @default.
• W2020698032 cites W2134648527 @default.
• W2020698032 cites W2140014095 @default.
• W2020698032 cites W2162725007 @default.
• W2020698032 cites W2167430418 @default.
• W2020698032 cites W2317111303 @default.
• W2020698032 cites W2414138909 @default.
• W2020698032 cites W2563968543 @default.
• W2020698032 cites W2608539973 @default.
• W2020698032 cites W4214589643 @default.
• W2020698032 cites W4379136709 @default.
• W2020698032 doi "https://doi.org/10.1046/j.1523-1755.2003.00718.x" @default.
• W2020698032 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12472772" @default.
• W2020698032 hasPublicationYear "2003" @default.
• W2020698032 type Work @default.
• W2020698032 sameAs 2020698032 @default.
• W2020698032 citedByCount "51" @default.
• W2020698032 countsByYear W20206980322012 @default.
• W2020698032 countsByYear W20206980322013 @default.
• W2020698032 countsByYear W20206980322014 @default.
• W2020698032 countsByYear W20206980322015 @default.
• W2020698032 countsByYear W20206980322016 @default.
• W2020698032 countsByYear W20206980322017 @default.
• W2020698032 countsByYear W20206980322018 @default.
• W2020698032 countsByYear W20206980322019 @default.
• W2020698032 countsByYear W20206980322020 @default.
• W2020698032 countsByYear W20206980322021 @default.
• W2020698032 countsByYear W20206980322022 @default.
• W2020698032 crossrefType "journal-article" @default.
• W2020698032 hasAuthorship W2020698032A5017265102 @default.
• W2020698032 hasAuthorship W2020698032A5028287367 @default.
• W2020698032 hasAuthorship W2020698032A5049295400 @default.
• W2020698032 hasAuthorship W2020698032A5062825190 @default.
• W2020698032 hasAuthorship W2020698032A5079089312 @default.
• W2020698032 hasAuthorship W2020698032A5081283954 @default.
• W2020698032 hasBestOaLocation W20206980321 @default.
• W2020698032 hasConcept C104950815 @default.
• W2020698032 hasConcept C126322002 @default.
• W2020698032 hasConcept C134018914 @default.
• W2020698032 hasConcept C134651460 @default.
• W2020698032 hasConcept C153911025 @default.
• W2020698032 hasConcept C181199279 @default.
• W2020698032 hasConcept C184235292 @default.
• W2020698032 hasConcept C185592680 @default.
• W2020698032 hasConcept C203565725 @default.
• W2020698032 hasConcept C2776329913 @default.
• W2020698032 hasConcept C2776914184 @default.
• W2020698032 hasConcept C2779415389 @default.
• W2020698032 hasConcept C55493867 @default.
• W2020698032 hasConcept C71924100 @default.
• W2020698032 hasConcept C86803240 @default.
• W2020698032 hasConcept C98274493 @default.
• W2020698032 hasConcept C99971728 @default.
• W2020698032 hasConceptScore W2020698032C104950815 @default.
• W2020698032 hasConceptScore W2020698032C126322002 @default.
• W2020698032 hasConceptScore W2020698032C134018914 @default.
• W2020698032 hasConceptScore W2020698032C134651460 @default.
• W2020698032 hasConceptScore W2020698032C153911025 @default.
• W2020698032 hasConceptScore W2020698032C181199279 @default.
• W2020698032 hasConceptScore W2020698032C184235292 @default.
• W2020698032 hasConceptScore W2020698032C185592680 @default.
• W2020698032 hasConceptScore W2020698032C203565725 @default.
• W2020698032 hasConceptScore W2020698032C2776329913 @default.

• next