PMID- 20525893
OWN - NLM
STAT- MEDLINE
DCOM- 20100901
LR  - 20181201
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 185
IP  - 1
DP  - 2010 Jul 1
TI  - Mechanisms of IL-12 synthesis by human dendritic cells treated with the chemical 
      sensitizer NiSO4.
PG  - 89-98
LID - 10.4049/jimmunol.0901992 [doi]
AB  - Allergic contact dermatitis, caused by metallic ions, is a T cell-mediated 
      inflammatory skin disease. IL-12 is a 70-kDa heterodimeric protein composed of 
      IL-12p40 and IL-12p35, playing a major role in the generation of 
      allergen-specific T cell responses. Dendritic cells (DCs) are APCs involved in 
      the induction of primary immune responses, as they possess the ability to 
      stimulate naive T cells. In this study, we address the question whether the 
      sensitizer nickel sulfate (NiSO(4)) itself or in synergy with other signals can 
      induce the secretion of IL-12p70 in human monocyte-derived DCs (Mo-DCs). We found 
      that IL-12p40 was produced by Mo-DC in response to NiSO(4) stimulation. Addition 
      of IFN-gamma concomitantly to NiSO(4) leads to IL-12p70 synthesis. NiSO(4) 
      treatment leads to the activation of MAPK, NF-kappaB pathways, and IFN regulatory 
      factor 1 (IRF-1). We investigated the role of these signaling pathways in IL-12 
      production using known pharmacological inhibitors of MAPK and NF-kappaB pathways 
      and RNA interference-mediated silencing of IRF-1. Our results showed that p38 
      MAPK, NF-kappaB, and IRF-1 were involved in IL-12p40 production induced by 
      NiSO(4). Moreover, IRF-1 silencing nearly totally abrogated IL-12p40 and IL-12p70 
      production provoked by NiSO(4) and IFN-gamma. In response to NiSO(4), we observed 
      that STAT-1 was phosphorylated on both serine and tyrosine residues and 
      participated to NiSO(4)-induced IRF-1 activation. N-acetylcysteine abolished 
      STAT-1 phosphorylation, suggesting that STAT-1 activation may be dependent on 
      NiSO(4)-induced alteration of the redox status of the cell. These results 
      indicate that p38 MAPK, NF-kappaB, and IRF-1 are activated by NiSO(4) in Mo-DC 
      and cooperate for IL-12 production.
FAU - Antonios, Diane
AU  - Antonios D
AD  - Universud, Institut National de la Sante et de la Recherche Medicale Unite Mixte 
      de Recherche S 749 and 996, Faculte de Pharmacie, Chatenay-Malabry, France.
FAU - Rousseau, Philippe
AU  - Rousseau P
FAU - Larange, Alexandre
AU  - Larange A
FAU - Kerdine-Romer, Saadia
AU  - Kerdine-Romer S
FAU - Pallardy, Marc
AU  - Pallardy M
LA  - eng
PT  - Journal Article
DEP - 20100604
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (IL12A protein, human)
RN  - 0 (Interferon Regulatory Factor-1)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-12 Subunit p35)
RN  - 0 (Interleukin-12 Subunit p40)
RN  - 0 (Irritants)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 187348-17-0 (Interleukin-12)
RN  - 4FLT4T3WUN (nickel sulfate)
RN  - 7OV03QG267 (Nickel)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Cells, Cultured
MH  - Dendritic Cells/enzymology/*immunology/*metabolism
MH  - Humans
MH  - Interferon Regulatory Factor-1/antagonists & inhibitors/metabolism/physiology
MH  - Interferon-gamma/physiology
MH  - Interleukin-1/*biosynthesis
MH  - Interleukin-12/biosynthesis/metabolism
MH  - Interleukin-12 Subunit p35/biosynthesis/genetics
MH  - Interleukin-12 Subunit p40/biosynthesis
MH  - Irritants/*toxicity
MH  - JNK Mitogen-Activated Protein Kinases/physiology
MH  - MAP Kinase Signaling System/immunology
MH  - Monocytes/enzymology/immunology/metabolism
MH  - NF-kappa B/antagonists & inhibitors/metabolism/physiology
MH  - Nickel/*toxicity
MH  - RNA, Messenger/biosynthesis
MH  - STAT1 Transcription Factor/physiology
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & 
      inhibitors/metabolism/physiology
EDAT- 2010/06/08 06:00
MHDA- 2010/09/02 06:00
CRDT- 2010/06/08 06:00
PHST- 2010/06/08 06:00 [entrez]
PHST- 2010/06/08 06:00 [pubmed]
PHST- 2010/09/02 06:00 [medline]
AID - jimmunol.0901992 [pii]
AID - 10.4049/jimmunol.0901992 [doi]
PST - ppublish
SO  - J Immunol. 2010 Jul 1;185(1):89-98. doi: 10.4049/jimmunol.0901992. Epub 2010 Jun 
      4.