title: LPS Up-Regulates Cystathionine γ -Lyase Gene Expression in Primary Human Macrophages via NF-κB/ERK Pathway.
abstract: Hydrogen sulfide (H2S) is an endogenous inflammatory mediator produced by the activity of cystathionine γ-lyase (CSE) in mammals. Macrophages are a key element of the immune system and play a crucial role in inflammation. To determine the role of H2S and macrophages in inflammation, we investigated the expression of CSE in human primary macrophages. Our results show that H2S is produced by the activity of CSE in these cells. To investigate the role of common signalling pathway in biosynthesis of CSE in human primary macrophages, specific inhibitors were used to block NF-κB, ERK, p38 and JNK. Inhibition of NF-κB, ERK significantly reduced levels of CSE gene and protein expression in these cells but inhibition of JNK and p38 did not have an inhibitory effect on the expression of CSE gene in macrophages. Inhibition of NF-κB and ERK prevented the effect of LPS on H2S synthesizing activity in human primary macrophages. These data showed that H2S acts as an inflammatory mediator via NF-κB/ERK pathway in macrophages.
authors.forename: Alireza
authors.initials: A
authors.lastname: Badiei
authors.forename: Steven
authors.initials: S
authors.lastname: Gieseg
authors.forename: Sian
authors.initials: S
authors.lastname: Davies
authors.forename: Mohd
authors.initials: M
authors.lastname: Izani Othman
authors.affiliation: Inflammation Research Group, Department of Pathology, University of Otago, Christchurch, 2 Riccarton Avenue, P.O. Box 4345, Christchurch 8140, New Zealand. madhav.bhatia@otago.ac.nz.
authors.forename: Madhav
authors.initials: M
authors.lastname: Bhatia
mesh_terms: D002478:Cells, Cultured; D003542:Cystathionine gamma-Lyase / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D061251:Primary Cell Culture; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide