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

Abstract

. Involvement of JAK2 and MAPK on type II nitric oxide synthase expression in skin-derived dendritic cells. Am. J. Physiol. 277 (Cell Physiol. 46): C1050-C1057, 1999.-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-␣ (TNF-␣) and granulocytemacrophage 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 LPSand GM-CSF-induced nitrite (NO 2 Ϫ ) production. The effect of LPS and cytokines on NO 2 Ϫ 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 Ϫ production evoked by LPS, TNF-␣, 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-␣ or GM-CSF on NO 2 Ϫ production. Immunocytochemistry studies revealed that the transcription factor nuclear factor-B 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.mitogen-activated protein kinase; Janus kinase 2; nuclear factor-B

The Ischemia-Responsive Protein 94 (Irp94) Activates Dendritic Cells through NK Cell Receptor Protein-2/NK Group 2 Member D (NKR-P2/NKG2D) Leading to Their Maturation

“…cIrp94-treated BMDCs show a strong translocation as compared with LPS in the nucleus, which suggests the early activation of NF-B with NKR-P2 ligation. NF-B activation takes place due to the phosphorylation and degradation of IB in the cytoplasm (77); data on cIrp94-mediated degradation of I〉␣ also support the involvement of NF-〉 activation during Irp94-NKR-P2 interaction. Thus, our data suggest NF-B to be a key executioner of Irp94-mediated activation of BMDCs.…”

“…The results from the studies with pharmacological inhibitors demonstrated that NO production with Irp94-NKR-P2 interaction is regulated by PI3K, tyrosine kinase, ERK kinase, serine threonine protein phosphatase, and protein kinase C. These observations suggest the involvement of a MAPK pathway in NKR-P2-mediated DC activation. Similar pathways seem to operate in DCs for iNOS induction (77) and with Hsp60 interaction in DCs (78). However, it will be interesting to investigate the accurate signal transduction cascade upon NKR-P2 ligation with Irp94.…”

Dexamethasone prevents granulocyte‐macrophage colony‐stimulating factor‐induced nuclear factor‐κB activation, inducible nitric oxide synthase expression and nitric oxide production in a skin dendritic cell line

“…21 The results indicated that there was no significant toxicity of dexamethasone in the concentrations used (data not shown).…”

“…19,20 We have previously shown, using a mouse fetal skin dendritic cell line (FSDC) in culture, that GM-CSF, a cytokine produced by allergen-stimulated keratinocytes that promotes Langerhans cell maturation and antigen presentation, induces NO production. 21 This is dependent on the expression of iNOS and is associated with the activation of the transcription nuclear factor kappa B (NF-kB). 22 This transcription factor is present in a latent (inactive) state in the cytoplasm, bound to an inhibitor, IkappaB (IkB).…”

Janus kinase 2 is involved in lipopolysaccharide-induced activation of macrophages

“…Stromal cell-derived factor (SDF)-1␣ stimulation via chemokine receptor CXCR4 led to the tyrosine phosphorylation of JAK2 in a human progenitor cell line and in human T cell lines (53, 57). JAK2 is involved in the expression of type II nitric oxide synthase (iNOS) in skin-derived dendritic cells treated with LPS (10).…”