title: Doxycycline inhibits TREM-1 induction by Porphyromonas gingivalis.
abstract: 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.
authors.affiliation: Oral Translational Research, Institute of Oral Biology, Center of Dental Medicine, University of Zürich, Switzerland. nagihan.bostanci@zzm.uzh.ch
authors.forename: Nagihan
authors.initials: N
authors.lastname: Bostanci
authors.forename: Georgios N
authors.initials: GN
authors.lastname: Belibasakis
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D004318:Doxycycline / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013997:Time Factors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D004318:Doxycycline