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Metabolism of nitric oxide by Neisseria meningitidis modifies release of NO-regulated cytokines and chemokines by human macrophages

Metabolism of nitric oxide by Neisseria meningitidis modifies release of NO-regulated cytokines and chemokines by human macrophages
Metabolism of nitric oxide by Neisseria meningitidis modifies release of NO-regulated cytokines and chemokines by human macrophages

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.

Chemokines, Cytokines, Gene Expression Regulation, Humans, Macrophages, Monocytes, Neisseria meningitidis, Nitric Oxide, Nitric Oxide Donors, Nitrite Reductases, Penicillamine, Phagocytosis, Journal Article, Research Support, Non-U.S. Gov't
1286-4579
981-987
Stevanin, Tânia M.
ff5fc52c-a001-42d6-9b01-3cb24e4758b1
Laver, Jay R.
b2996398-2ccf-40f0-92b8-f338f3de796b
Poole, Robert K.
5f1f3b79-cf45-4ae6-89cd-e4259c03ae56
Moir, James W.B.
f6831b5f-5cfd-4c56-b3cd-6782f413a07f
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Stevanin, Tânia M.
ff5fc52c-a001-42d6-9b01-3cb24e4758b1
Laver, Jay R.
b2996398-2ccf-40f0-92b8-f338f3de796b
Poole, Robert K.
5f1f3b79-cf45-4ae6-89cd-e4259c03ae56
Moir, James W.B.
f6831b5f-5cfd-4c56-b3cd-6782f413a07f
Read, Robert C.
b5caca7b-0063-438a-b703-7ecbb6fc2b51

Stevanin, Tânia M., Laver, Jay R., Poole, Robert K., Moir, James W.B. and Read, Robert C. (2007) Metabolism of nitric oxide by Neisseria meningitidis modifies release of NO-regulated cytokines and chemokines by human macrophages. Microbes and infection, 9 (8), 981-987. (doi:10.1016/j.micinf.2007.04.002).

Record type: Article

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.

Full text not available from this repository.

More information

Accepted/In Press date: 2 April 2007
e-pub ahead of print date: 11 April 2007
Published date: July 2007
Keywords: Chemokines, Cytokines, Gene Expression Regulation, Humans, Macrophages, Monocytes, Neisseria meningitidis, Nitric Oxide, Nitric Oxide Donors, Nitrite Reductases, Penicillamine, Phagocytosis, Journal Article, Research Support, Non-U.S. Gov't

Identifiers

Local EPrints ID: 416282
URI: https://eprints.soton.ac.uk/id/eprint/416282
ISSN: 1286-4579
PURE UUID: 1a400869-8980-4030-939f-3cfcd0178f7d
ORCID for Robert C. Read: ORCID iD orcid.org/0000-0002-4297-6728

Catalogue record

Date deposited: 11 Dec 2017 17:30
Last modified: 14 Mar 2019 01:36

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