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Th1-type immune responses to Porphyromonas gingivalis antigens exacerbate angiotensin II-dependent hypertension and vascular dysfunction

dc.contributor.authorCzesnikiewicz-Guzik, Marta
dc.contributor.authorNosalski, Ryszard
dc.contributor.authorMikolajczyk, Tomasz P.
dc.contributor.authorVidler, Francesca
dc.contributor.authorDohnal, Tomasz
dc.contributor.authorDembowska, Elzbieta
dc.contributor.authorGraham, Delyth
dc.contributor.authorHarrison, David G.
dc.contributor.authorGuzik, Tomasz J.
dc.date.accessioned2020-09-24T13:28:01Z
dc.date.available2020-09-24T13:28:01Z
dc.date.issued2019-06
dc.identifier.citationCzesnikiewicz-Guzik, M., Nosalski, R., Mikolajczyk, T. P., Vidler, F., Dohnal, T., Dembowska, E., Graham, D., Harrison, D. G., & Guzik, T. J. (2019). Th1-type immune responses to Porphyromonas gingivalis antigens exacerbate angiotensin II-dependent hypertension and vascular dysfunction. British journal of pharmacology, 176(12), 1922–1931. https://doi.org/10.1111/bph.14536en_US
dc.identifier.issn0007-1188
dc.identifier.othereISSN: 1476-5381
dc.identifier.urihttp://hdl.handle.net/1803/16153
dc.description.abstractBackground and Purpose Emerging evidence indicates that hypertension is mediated by immune mechanisms. We hypothesized that exposure to Porphyromonas gingivalis antigens, commonly encountered in periodontal disease, can enhance immune activation in hypertension and exacerbate the elevation in BP, vascular inflammation and vascular dysfunction. Experimental Approach Th1 immune responses were elicited through immunizations using P. gingivalis lysate antigens (10 mu g) conjugated with aluminium oxide (50 mu g) and IL-12 (1 mu g). The hypertension and vascular endothelial dysfunction evoked by subpressor doses of angiotensin II (0.25 mg center dot kg(-1)center dot day(-1)) were studied, and vascular inflammation was quantified by flow cytometry and real-time PCR. Key Results Systemic T-cell activation, a characteristic of hypertension, was exacerbated by P. gingivalis antigen stimulation. This translated into increased aortic vascular inflammation with enhanced leukocyte, in particular, T-cell and macrophage infiltration. The expression of the Th1 cytokines, IFN-gamma and TNF-alpha, and the transcription factor, TBX21, was increased in aortas of P. gingivalis/IL-12/aluminium oxide-immunized mice, while IL-4 and TGF-beta were unchanged. These immune changes in mice with induced T-helper-type 1 immune responses were associated with an enhanced elevation of BP and endothelial dysfunction compared with control mice in response to 2 week infusion of a subpressor dose of angiotensin II. Conclusions and Implications These results support the concept that Th1 immune responses induced by bacterial antigens such as P. gingivalis can increase sensitivity to subpressor pro-hypertensive insults such as low-dose angiotensin II, thus providing a mechanistic link between chronic infection, such as periodontitis, and hypertension. Linked Articles This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visiten_US
dc.description.sponsorshipThe paper is supported by the Marie Curie CIG (no. 631773), European Research Council (726318 to T.J.G.) as well as the BHF Centre of Research Excellence (RE/13/5/30177), National Institutes of Health (NIH) grants HL-390006, AR-42527, AI-44142, EY-11916 and AR-41974 and NIH Program Project grants HL-58000 and P01075209.en_US
dc.language.isoen_USen_US
dc.publisherBritish Journal of Pharmacologyen_US
dc.rightsCopyright © 2018 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.source.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534780/
dc.subjectCD8(+) T-CELLSen_US
dc.subjectBLOOD-PRESSUREen_US
dc.subjectPERIODONTAL PATHOGENSen_US
dc.subjectINTERFERON-GAMMAen_US
dc.subjectASSOCIATIONen_US
dc.subjectACTIVATIONen_US
dc.subjectPROLIFERATIONen_US
dc.subjectACCUMULATIONen_US
dc.subjectINFLAMMATIONen_US
dc.subjectEXPRESSIONen_US
dc.titleTh1-type immune responses to Porphyromonas gingivalis antigens exacerbate angiotensin II-dependent hypertension and vascular dysfunctionen_US
dc.typeArticleen_US
dc.identifier.doi10.1111/bph.14536


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