| First Author | Cruz MT | Year | 1999 |
| Journal | Am J Physiol | Volume | 277 |
| Issue | 6 Pt 1 | Pages | C1050-7 |
| PubMed ID | 10600756 | Mgi Jnum | J:172914 |
| Mgi Id | MGI:5009205 | Doi | 10.1152/ajpcell.1999.277.6.C1050 |
| Citation | Cruz MT, et al. (1999) Involvement of JAK2 and MAPK on type II nitric oxide synthase expression in skin-derived dendritic cells. Am J Physiol 277(6 Pt 1):C1050-7 |
| abstractText | 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. |
