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Suppression of inflammatory gene expression in T cells by Porphyromonas gingivalis is mediated by targeting MAPK signaling

Cellular & Molecular Immunology volume 10, pages 413–422 (2013)Cite this article

Abstract

There is increasing awareness of the effects of Porphyromonas gingivalis on host immune responses. Degradation of cytokines and chemokines by cysteine proteinases has previously been reported. However, the precise mechanisms by which P. gingivalis is able to alter intracellular signaling, and thus proliferation and inflammation, have not been described. We have previously reported suppression of activator protein-1 (AP-1) and degradation of IL-2 by proteinases from P. gingivalis. In the present study, we have analyzed the effects of P. gingivalis on Jurkat T-cell signal transduction and subsequent IL-2 and CXCL8 expression. We found that CXCL8, but not IL-2, gene expression levels were significantly suppressed by viable P. gingivalis. Analysis of intracellular signaling revealed an inhibitory effect of P. gingivalis on c-Jun and c-Fos, but not NFκB (p50 and p65), NFAT or STAT5 expression. This inhibitory effect was not due to suppression of mitogen-activated protein kinase (MAPK) (p38, erk and JNK) gene expression, but was rather due to prevention of protein kinase C (PKC) and p38 phosphorylation, as demonstrated by western blot analysis. Furthermore, SOCS1 and SOCS3 expression levels decreased following treatment of Jurkat T cells with viable P. gingivalis. The results indicate that P. gingivalis is able to suppress inflammatory gene expression by targeting the activity of MAPK pathways in T cells, which was confirmed by using specific inhibitors of NF-κB, PKC, ERK, p38 and JNK.

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Acknowledgements

This work was supported by grants from the Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Fund for Research without Animal Experiments, the Swedish Heart and Lung Association, the Foundation of Olle Engkvist and the Foundation of Längmanska Kulturfonden.

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  1. Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden

    Hazem Khalaf, Isak Demirel & Torbjörn Bengtsson

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Correspondence to Hazem Khalaf.

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Khalaf, H., Demirel, I. & Bengtsson, T. Suppression of inflammatory gene expression in T cells by Porphyromonas gingivalis is mediated by targeting MAPK signaling. Cell Mol Immunol 10, 413–422 (2013). https://doi.org/10.1038/cmi.2013.23

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