title: Nitric oxide affects IL-6 expression in human peripheral blood mononuclear cells involving cGMP-dependent modulation of NF-κB activity.
abstract: Interleukin 6 (IL-6) and nitric oxide (NO) are important mediators of the inflammatory response. We report that in human peripheral blood mononuclear cells (PBMCs), NO exerts a biphasic effect on the expression of IL-6. Using sodium nitroprusside (SNP) and S-nitrosoglutathione (GSNO) as NO-donating compounds, we observed that both mRNA and protein levels of IL-6 increased at lower (≤10μM) and decreased at higher (>100μM) concentrations of NO donors. Changes in the expression of IL-6 correlated with changes in the activity of NF-κB, which increased at lower and decreased at higher concentrations of both NO donors as shown by the electrophoretic mobility shift assay (EMSA). The effects of NO on NF-κB activity were cGMP-dependent because they were reversed in the presence of ODQ, the inhibitor of soluble guanylyl cyclase (sGC), and KT5823, the inhibitor of cGMP-dependent protein kinase (PKG). Moreover, the membrane permeable analog of cGMP (8-Br-cGMP) mimicked the effect of the NO donors. These observations show that NO, depending on its concentration, may act in human PBMCs as a stimulator of IL-6 expression involving the sGC/cGMP/PKG pathway.
authors.affiliation: Laboratory of Signaling Proteins, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, 53-114 Wrocław, Poland. siednienko@iitd.pan.wroc.pl
authors.forename: Jakub
authors.initials: J
authors.lastname: Siednienko
authors.forename: Joanna
authors.initials: J
authors.lastname: Nowak
authors.forename: Paul N
authors.initials: PN
authors.lastname: Moynagh
authors.forename: Wojciech A
authors.initials: WA
authors.lastname: Gorczyca
mesh_terms: D002227:Carbazoles / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000378:metabolism; D026422:S-Nitrosoglutathione / Q000378:metabolism
chemical_list: D002227:Carbazoles; D016207:Cytokines; D015850:Interleukin-6; D016328:NF-kappa B; D020030:Nitric Oxide Donors; C073601:KT 5823; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D006152:Cyclic GMP