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

Cell Mol Immunol. 2013 Sep;10(5):413-22. doi: 10.1038/cmi.2013.23. Epub 2013 Jul 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coculture Techniques
  • Down-Regulation
  • Gene Expression / immunology*
  • Genes, fos / genetics
  • Genes, fos / immunology
  • Humans
  • Inflammation / immunology
  • Inflammation / microbiology
  • Inflammation / pathology
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / immunology
  • Jurkat Cells
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / immunology*
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Phosphorylation
  • Porphyromonas gingivalis / physiology*
  • Protein Kinase C / genetics
  • Protein Kinase C / immunology
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Suppressor of Cytokine Signaling Proteins / immunology
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / immunology

Substances

  • Interleukin-2
  • Interleukin-8
  • NF-kappa B
  • SOCS1 protein, human
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Protein Kinase C
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases