Involvement of JAK2 and MAPK on type II nitric oxide synthase expression in skin-derived dendritic cells

In this report, we demonstrate that a fetal mouse skin-derived dendritic cell line produces nitric oxide (NO) in response to the endotoxin [lipopolysaccharide (LPS)] and to cytokines [tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF)]. Expression of the inducible isoform of NO synthase (iNOS) was confirmed by immunofluorescence with an antibody against iNOS. The tyrosine kinase inhibitor genistein decreased LPS- and GM-CSF-induced nitrite (NO(-2)) production. The effect of LPS and cytokines on NO(-2) production was inhibited by the Janus kinase 2 (JAK2) inhibitor tyrphostin B42. The p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB-203580 also reduced the NO(-2) production evoked by LPS, TNF-alpha, or GM-CSF, but it was not as effective as tyrphostin B42. Inhibition of MAPK kinase with PD-098059 also slightly reduced the effect of TNF-alpha or GM-CSF on NO(-2) production. Immunocytochemistry studies revealed that the transcription factor nuclear factor-kappaB was translocated from the cytoplasm into the nuclei of fetal skin-derived dendritic cells (FSDC) stimulated with LPS, and this translocation was inhibited by tyrphostin B42. Our results show that JAK2 plays a major role in the induction of iNOS in FSDC.

Medienart:

E-Artikel

Erscheinungsjahr:

1999

Erschienen:

1999

Enthalten in:

Zur Gesamtaufnahme - volume:277

Enthalten in:

The American journal of physiology - 277(1999), 6 vom: 17. Dez., Seite C1050-7

Sprache:

Englisch

Beteiligte Personen:

Cruz, M T [VerfasserIn]
Duarte, C B [VerfasserIn]
Gonçalo, M [VerfasserIn]
Carvalho, A P [VerfasserIn]
Lopes, M C [VerfasserIn]

Links:

Volltext

Themen:

2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
83869-56-1
Alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
DH2M523P0H
EC 1.14.13.39
EC 2.7.10.1
EC 2.7.10.2
EC 2.7.11.24
Enzyme Inhibitors
Flavonoids
Genistein
Granulocyte-Macrophage Colony-Stimulating Factor
Imidazoles
Interleukin-1
Jak2 protein, mouse
Janus Kinase 2
Journal Article
Lipopolysaccharides
Mitogen-Activated Protein Kinases
NF-kappa B
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nos2 protein, mouse
OU13V1EYWQ
P38 Mitogen-Activated Protein Kinases
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
Pyridines
Research Support, Non-U.S. Gov't
SB 203580
SJE1IO5E3I
Tumor Necrosis Factor-alpha
Tyrphostins

Anmerkungen:

Date Completed 20.01.2000

Date Revised 20.09.2018

published: Print

Citation Status MEDLINE

doi:

10.1152/ajpcell.1999.277.6.C1050

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM10530543X