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Hydrogen sulfide induces the synthesis of proinflammatory cytokines in human monocyte cell line U937 via the ERK-NF-kappaB pathway.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 2007 May; Vol. 81 (5), pp. 1322-32. Date of Electronic Publication: 2007 Feb 08. - Publication Year :
- 2007
-
Abstract
- Hydrogen sulfide (H2S) is now considered an endogenous, gaseous mediator, which has been demonstrated to be involved in many inflammatory states. However, the mechanism of its proinflammatory function remains unknown. In the present study, we used IFN-gamma-primed human monocytic cell line U937 to investigate the effects of H2S in vitro on monocytes. We found that treatment with the H2S donor, sodium hydrosulfide, led to significant increases in the mRNA expression and protein production of TNF-alpha, IL-1beta, and IL-6 in U937 cells. H2S-triggered monocyte activation was confirmed further by the up-regulation of CD11b expression on the cell surface. We also observed that H2S could induce a rapid degradation of IkappaBalpha and subsequent activation of NF-kappaB p65, and this effect was attenuated by Bay 11-7082, a specific inhibitor of NF-kappaB. Furthermore, pretreatment of cells with Bay 11-7082 substantially inhibited the secretion of TNF-alpha, IL-1beta, and IL-6 induced by H2S. We also found that H2S stimulated the phosphorylation and activation of ERK1/2, but not of p38 MAPK and JNK, and pretreatment with PD98059, a selective MEK1 antagonist, could inhibit H2S-induced NF-kappaB activation markedly. Together, our findings suggest for the first time that H2S stimulates the activation of human monocytes with the generation of proinflammatory cytokines, and this response is, at least partially, through the ERK-NF-kappaB signaling pathway.
- Subjects :
- CD11b Antigen biosynthesis
CD11b Antigen drug effects
Cell Line
Cytokines genetics
Dose-Response Relationship, Drug
Extracellular Signal-Regulated MAP Kinases immunology
Flavonoids pharmacology
Gene Expression Profiling
Humans
I-kappa B Proteins drug effects
I-kappa B Proteins immunology
Inflammation chemically induced
Monocytes immunology
NF-KappaB Inhibitor alpha
NF-kappa B antagonists & inhibitors
NF-kappa B drug effects
Nitriles pharmacology
Phosphorylation
RNA, Messenger biosynthesis
RNA, Messenger drug effects
RNA, Messenger genetics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction drug effects
Signal Transduction immunology
Structure-Activity Relationship
Sulfides antagonists & inhibitors
Sulfones pharmacology
Time Factors
Up-Regulation drug effects
Cytokines biosynthesis
Cytokines drug effects
Extracellular Signal-Regulated MAP Kinases drug effects
Monocytes drug effects
NF-kappa B immunology
Sulfides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0741-5400
- Volume :
- 81
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 17289797
- Full Text :
- https://doi.org/10.1189/jlb.1006599