Inhibited Production of iNOS by Murine J774 Macrophages Occurs via a phoP-Regulated Differential Expression of NFκB and AP-1
Background. There are no reported data to explain how Salmonella suppress nitrite ion production in macrophages or whether this phenomenon is unique to typhoidal or non-typhoidal serovars. The aims of this study were, therefore, to investigate these phenomena. Methods. We measured survival of S. typ...
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| Format: | Article |
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Wiley
2012-01-01
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| Series: | Interdisciplinary Perspectives on Infectious Diseases |
| Online Access: | http://dx.doi.org/10.1155/2012/483170 |
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| author | Scott D. Hulme Paul A. Barrow Neil Foster |
| author_facet | Scott D. Hulme Paul A. Barrow Neil Foster |
| author_sort | Scott D. Hulme |
| collection | DOAJ |
| description | Background. There are no reported data to explain how Salmonella suppress nitrite ion production in macrophages or whether this phenomenon is unique to typhoidal or non-typhoidal serovars. The aims of this study were, therefore, to investigate these phenomena. Methods. We measured survival of S. typhimurium 14028 and its phoP mutant in murine J774 macrophages, cultured with or without interferon gamma. We compared expression of inducible nitric oxide synthase (iNOS) mRNA and protein, and nitrite ion production and also examined binding of nuclear factor 𝜅B (NF𝜅B) and activator protein 1 (AP-1) to macrophage DNA. Results. S. typhimurium 14028 inhibited binding of NF𝜅B and AP-1 to DNA in murine J774. A macrophages via an intact phoP regulon. This correlated with increased survival and reduced iNOS expression. Suppression of NF𝜅B activity was ameliorated in macrophages cultured with IFN-γ and this correlated with increased expression of iNOS mRNA and nitrite ion production, although IFN-γ had no effect on AP-1/DNA interaction. We show, that with one exception, suppression of iNOS is unique to typhoidal serovars. Conclusion. S. typhimurium inhibit NF𝜅B and AP-1 interaction with macrophage DNA via the PhoP regulon, this reduces nitrite ion production and is principally associated with typhoidal serovars. |
| format | Article |
| id | doaj-art-47d65be44a714258abdd77988c1e2d94 |
| institution | OA Journals |
| issn | 1687-708X 1687-7098 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Interdisciplinary Perspectives on Infectious Diseases |
| spelling | doaj-art-47d65be44a714258abdd77988c1e2d942025-08-20T02:37:54ZengWileyInterdisciplinary Perspectives on Infectious Diseases1687-708X1687-70982012-01-01201210.1155/2012/483170483170Inhibited Production of iNOS by Murine J774 Macrophages Occurs via a phoP-Regulated Differential Expression of NFκB and AP-1Scott D. Hulme0Paul A. Barrow1Neil Foster2School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, Nottingham NG7 2NR, UKSchool of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, Nottingham NG7 2NR, UKSchool of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, Nottingham NG7 2NR, UKBackground. There are no reported data to explain how Salmonella suppress nitrite ion production in macrophages or whether this phenomenon is unique to typhoidal or non-typhoidal serovars. The aims of this study were, therefore, to investigate these phenomena. Methods. We measured survival of S. typhimurium 14028 and its phoP mutant in murine J774 macrophages, cultured with or without interferon gamma. We compared expression of inducible nitric oxide synthase (iNOS) mRNA and protein, and nitrite ion production and also examined binding of nuclear factor 𝜅B (NF𝜅B) and activator protein 1 (AP-1) to macrophage DNA. Results. S. typhimurium 14028 inhibited binding of NF𝜅B and AP-1 to DNA in murine J774. A macrophages via an intact phoP regulon. This correlated with increased survival and reduced iNOS expression. Suppression of NF𝜅B activity was ameliorated in macrophages cultured with IFN-γ and this correlated with increased expression of iNOS mRNA and nitrite ion production, although IFN-γ had no effect on AP-1/DNA interaction. We show, that with one exception, suppression of iNOS is unique to typhoidal serovars. Conclusion. S. typhimurium inhibit NF𝜅B and AP-1 interaction with macrophage DNA via the PhoP regulon, this reduces nitrite ion production and is principally associated with typhoidal serovars.http://dx.doi.org/10.1155/2012/483170 |
| spellingShingle | Scott D. Hulme Paul A. Barrow Neil Foster Inhibited Production of iNOS by Murine J774 Macrophages Occurs via a phoP-Regulated Differential Expression of NFκB and AP-1 Interdisciplinary Perspectives on Infectious Diseases |
| title | Inhibited Production of iNOS by Murine J774 Macrophages Occurs via a phoP-Regulated Differential Expression of NFκB and AP-1 |
| title_full | Inhibited Production of iNOS by Murine J774 Macrophages Occurs via a phoP-Regulated Differential Expression of NFκB and AP-1 |
| title_fullStr | Inhibited Production of iNOS by Murine J774 Macrophages Occurs via a phoP-Regulated Differential Expression of NFκB and AP-1 |
| title_full_unstemmed | Inhibited Production of iNOS by Murine J774 Macrophages Occurs via a phoP-Regulated Differential Expression of NFκB and AP-1 |
| title_short | Inhibited Production of iNOS by Murine J774 Macrophages Occurs via a phoP-Regulated Differential Expression of NFκB and AP-1 |
| title_sort | inhibited production of inos by murine j774 macrophages occurs via a phop regulated differential expression of nfκb and ap 1 |
| url | http://dx.doi.org/10.1155/2012/483170 |
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