PMID- 19238528 OWN - NLM STAT- MEDLINE DCOM- 20090617 LR - 20220409 IS - 1573-2576 (Electronic) IS - 0360-3997 (Linking) VI - 32 IP - 2 DP - 2009 Apr TI - Tetracyclines and chemically modified tetracycline-3 (CMT-3) modulate cytokine secretion by lipopolysaccharide-stimulated whole blood. PG - 130-7 LID - 10.1007/s10753-009-9111-9 [doi] AB - In addition to their bacteriostatic effect, tetracyclines, which are often used in the treatment of periodontitis, also present anti-inflammatory properties. In the present study, we investigated the effects of tetracycline (TC), doxycycline (doxy), and chemically modified tetracycline-3 (CMT-3) on the production of pro-inflammatory mediators and matrix metalloproteinases (MMPs) in an ex vivo human whole blood (WB) model stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). WB samples obtained from three periodontitis patients and six healthy subjects were stimulated with P. gingivalis LPS in the absence and presence of TC, doxy, or CMT-3. The secretion of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), MMP-8, and MMP-9 by the WB samples was determined using enzyme-linked immunosorbent assays. P. gingivalis LPS significantly increased the secretion of all cytokines and MMPs tested. While we observed inter-patient variations, TC, doxy, and CMT-3 caused reductions of LPS-induced cytokine secretion to various degrees. TC, doxy, and CMT-3 had no significant effect on MMP-8 and MMP-9 secretion by LPS-stimulated WB samples. In conclusion, we used a human WB model that takes into consideration relevant in vivo immune cell interactions in the presence of plasma proteins to show that TC, doxy, and CMT-3 can reduce the production of pro-inflammatory mediators. This property may contribute to the clinically proven benefits of these molecules in the treatment of periodontitis and other chronic inflammatory diseases. FAU - Cazalis, Julia AU - Cazalis J AD - Groupe de Recherche en Ecologie Buccale, Faculte de Medecine Dentaire, Universite Laval, Quebec City, Quebec, G1K 7P4, Canada. FAU - Tanabe, Shin-ichi AU - Tanabe S FAU - Gagnon, Guy AU - Gagnon G FAU - Sorsa, Timo AU - Sorsa T FAU - Grenier, Daniel AU - Grenier D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Inflammation JT - Inflammation JID - 7600105 RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 0 (Tetracyclines) RN - 0 (tetracycline CMT-3) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - F8VB5M810T (Tetracycline) RN - N12000U13O (Doxycycline) SB - IM MH - Blood/*drug effects/immunology MH - Cytokines/drug effects/*metabolism MH - Doxycycline/pharmacology MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Inflammation Mediators MH - Lipopolysaccharides/*pharmacology MH - Matrix Metalloproteinases/biosynthesis MH - Porphyromonas gingivalis MH - Tetracycline/*pharmacology MH - Tetracyclines/*pharmacology MH - Up-Regulation/drug effects EDAT- 2009/02/25 09:00 MHDA- 2009/06/18 09:00 CRDT- 2009/02/25 09:00 PHST- 2009/02/25 09:00 [entrez] PHST- 2009/02/25 09:00 [pubmed] PHST- 2009/06/18 09:00 [medline] AID - 10.1007/s10753-009-9111-9 [doi] PST - ppublish SO - Inflammation. 2009 Apr;32(2):130-7. doi: 10.1007/s10753-009-9111-9.