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Interdisciplinary Perspectives on Infectious Diseases
Volume 2012, Article ID 483170, 8 pages
Research Article

Inhibited Production of iNOS by Murine J774 Macrophages Occurs via a phoP-Regulated Differential Expression of NFκB and AP-1

School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire, Nottingham NG7 2NR, UK

Received 15 February 2012; Revised 10 May 2012; Accepted 21 May 2012

Academic Editor: Decio Diament

Copyright © 2012 Scott D. Hulme et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 𝜅 B (NF 𝜅 B) and activator protein 1 (AP-1) to macrophage DNA. Results. S. typhimurium 14028 inhibited binding of NF 𝜅 B 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 NF 𝜅 B 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 NF 𝜅 B and AP-1 interaction with macrophage DNA via the PhoP regulon, this reduces nitrite ion production and is principally associated with typhoidal serovars.