%0 Journal Article %1 stevanin_metabolism_2007 %A Stevanin, Tânia M %A Laver, Jay R %A Poole, Robert K %A Moir, James W B %A Read, Robert C %D 2007 %J Microbes and Infection / Institut Pasteur %K Chemokines, Cytokines, Donors, Expression Gene Humans, Macrophages, Monocytes, Neisseria Nitric Nitrite Oxide Oxide, Penicillamine, Phagocytosis Reductases, Regulation, meningitidis, %N 8 %P 981--7 %R S1286-4579(07)00163-3 %T Metabolism of nitric oxide by Neisseria meningitidis modifies release of NO-regulated cytokines and chemokines by human macrophages %U http://www.ncbi.nlm.nih.gov/pubmed/17544805 %V 9 %X Macrophages produce nitric oxide (NO) via the inducible nitric oxide synthase as part of a successful response to infection. The gene norB of Neisseria meningitidis encodes a NO reductase which enables utilization and consumption of NO during microaerobic respiration and confers resistance to nitrosative stress-related killing by human monocyte-derived macrophages (MDM). In this study we confirmed that NO regulates cytokine and chemokine release by resting MDM: accumulation of TNF-alpha, IL-12, IL-10, CCL5 (RANTES) and CXCL8 (IL-8) in MDM supernatants was significantly modified by the NO-donor S-nitroso-N-penicillamine (SNAP). Using a protein array, infection of MDM with N. meningitidis was shown to be associated with secretion of a wide range of cytokines and chemokines. To test whether NO metabolism by N. meningitidis modifies release of NO-regulated cytokines, we infected MDM with wild-type organisms and an isogenic norB strain. Resulting expression of the cytokines TNF-alpha and IL-12, and the chemokine CXCL8 was increased and production of the cytokine IL-10 and the chemokine CCL5 was decreased in norB-infected MDM, in comparison to wild-type. Addition of SNAP to cultures infected with wild-type mimicked the effect observed in cultures infected with the norB mutant. In conclusion, NorB-catalysed removal of NO modifies cellular release of NO-regulated cytokines and chemokines.

@article{stevanin_metabolism_2007, abstract = {Macrophages produce nitric oxide {(NO)} via the inducible nitric oxide synthase as part of a successful response to infection. The gene {norB} of Neisseria meningitidis encodes a {NO} reductase which enables utilization and consumption of {NO} during microaerobic respiration and confers resistance to nitrosative stress-related killing by human monocyte-derived macrophages {(MDM).} In this study we confirmed that {NO} regulates cytokine and chemokine release by resting {MDM:} accumulation of {TNF-alpha,} {IL-12,} {IL-10,} {CCL5} {(RANTES)} and {CXCL8} {(IL-8)} in {MDM} supernatants was significantly modified by the {NO-donor} {S-nitroso-N-penicillamine} {(SNAP).} Using a protein array, infection of {MDM} with N. meningitidis was shown to be associated with secretion of a wide range of cytokines and chemokines. To test whether {NO} metabolism by N. meningitidis modifies release of {NO-regulated} cytokines, we infected {MDM} with wild-type organisms and an isogenic {norB} strain. Resulting expression of the cytokines {TNF-alpha} and {IL-12,} and the chemokine {CXCL8} was increased and production of the cytokine {IL-10} and the chemokine {CCL5} was decreased in {norB-infected} {MDM,} in comparison to wild-type. Addition of {SNAP} to cultures infected with wild-type mimicked the effect observed in cultures infected with the {norB} mutant. In conclusion, {NorB-catalysed} removal of {NO} modifies cellular release of {NO-regulated} cytokines and chemokines.}, added-at = {2011-03-11T10:05:34.000+0100}, author = {Stevanin, Tânia M and Laver, Jay R and Poole, Robert K and Moir, James W B and Read, Robert C}, biburl = {https://www.bibsonomy.org/bibtex/2b0457a3181b0e13ac32bf4c0492f1d0a/jelias}, doi = {S1286-4579(07)00163-3}, interhash = {c7d13e654d1c280db2073aa5e6ce014e}, intrahash = {b0457a3181b0e13ac32bf4c0492f1d0a}, issn = {1286-4579}, journal = {Microbes and Infection / Institut Pasteur}, keywords = {Chemokines, Cytokines, Donors, Expression Gene Humans, Macrophages, Monocytes, Neisseria Nitric Nitrite Oxide Oxide, Penicillamine, Phagocytosis Reductases, Regulation, meningitidis,}, month = jul, note = {{PMID:} 17544805}, number = 8, pages = {981--7}, timestamp = {2011-03-11T10:05:51.000+0100}, title = {Metabolism of nitric oxide by Neisseria meningitidis modifies release of {NO-regulated} cytokines and chemokines by human macrophages}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17544805}, volume = 9, year = 2007 }