Doxycycline inhibits TREM-1 induction by Porphyromonas gingivalis

FEMS Immunol Med Microbiol. 2012 Oct;66(1):37-44. doi: 10.1111/j.1574-695X.2012.00982.x. Epub 2012 May 21.


The triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, with the capacity to amplify pro-inflammatory cytokine production. Porphyromonas gingivalis is a Gram-negative anaerobic species highly implicated in inflammatory periodontal disease, with potential involvement in systemic inflammation. Porphyromonas gingivalis positively regulates TREM-1 expression and production in monocytic cells. Subantimicrobial doses of doxycycline (SDD) are used as an adjunct treatment in periodontal therapy, because of their anti-inflammatory properties. The aim of this study was to investigate the effect of SDD on P. gingivalis-induced TREM-1 expression and secretion by the myelomonocytic cell line MonoMac-6. After 24 h of challenge, P. gingivalis enhanced TREM-1 gene expression by the cells, with a concomitant increase in soluble TREM-1 release. Nevertheless, SDD concentrations between 2 and 10 μg mL(-1) abolished TREM-1 expression and release, already after 4 h of administration. Moreover, SDD reduced P. gingivalis-induced interleukin-8 secretion, confirming its anti-inflammatory effects. In conclusion, SDD inhibits bacterially induced TREM-1, and this effect may partly account for its generalized anti-inflammatory properties. This could partly explain the clinical efficacy of SDD as an adjunctive treatment for periodontal disease, but may also indicate that SDD could serve as a suitable modulator of systemic inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Cell Line
  • Doxycycline / pharmacology*
  • Gene Expression Profiling
  • Humans
  • Immunologic Factors / pharmacology*
  • Interleukin-8 / metabolism
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / metabolism
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / microbiology*
  • Porphyromonas gingivalis / immunology*
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / biosynthesis
  • Time Factors
  • Triggering Receptor Expressed on Myeloid Cells-1


  • Anti-Bacterial Agents
  • Immunologic Factors
  • Interleukin-8
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • TREM1 protein, human
  • Triggering Receptor Expressed on Myeloid Cells-1
  • Doxycycline