Marie Dubar1,2, Kevin Carrasco3, Sebastien Gibot4,5, Catherine Bisson2,6. 1. Department of Periodontology, School of Dentistry, Lille University Hospital, Lille, France. 2. EA SIMPA 7300, University of Lorraine, Nancy, France. 3. INOTREM, Vandœuvre-Lès-Nancy, France. 4. Medical Intensive Care Unit, Hôpital Central, Nancy University Hospital, Nancy, France. 5. Inserm UMR_S1116, University of Lorraine, Nancy, France. 6. Department de Periodontology, University of Hospital, University of Lorraine, Nancy, France.
Abstract
Periodontal disease involves the activation of host immune response, acting not only as defender of periodontal tissues against bacterial aggression but also as mediator of tissue destruction. Triggering receptor expressed on myeloid cells 1 (TREM-1) is an immune receptor that synergizes with Toll-like receptors in amplifying the inflammatory response mediated by microbial molecules. AIM: To investigate the role of P. gingivalis lipopolysaccharide (LPS) and the effect of LR12, a TREM-1 inhibitory peptide, on the expression of membrane-bound and soluble form of TREM-1 on human primary monocytes, as well as the production of proinflammatory cytokines. MATERIAL AND METHODS: Cells were stimulated with 1 μg/ml of LPS with or without LR12. PCR, flow cytometry and ELISA were used to determine TREM-1 expressions and cytokines release by monocytes. RESULTS: P. gingivalis LPS can induce a significant increase in TREM-1 expression (mRNA, membrane-bound and soluble form, p < 0.001) as well as cytokines (IL-1β, TNFα) and chemokines (IL-8) production by monocytes. This monocytes' activation was partly prevented by LR12. CONCLUSIONS: TREM-1 inhibitors such as LR12 could be interesting for the modulation of the excessive inflammatory response that occurs during periodontal disease.
Periodontal disease involves the activation of host immune response, acting not only as defender of periodontal tissues against bacterial aggression but also as mediator of tissue destruction. Triggering receptor expressed on myeloid cells 1 (TREM-1) is an immune receptor that synergizes with Toll-like receptors in amplifying the inflammatory response mediated by microbial molecules. AIM: To investigate the role of P. gingivalis lipopolysaccharide (LPS) and the effect of LR12, a TREM-1 inhibitory peptide, on the expression of membrane-bound and soluble form of TREM-1 on human primary monocytes, as well as the production of proinflammatory cytokines. MATERIAL AND METHODS: Cells were stimulated with 1 μg/ml of LPS with or without LR12. PCR, flow cytometry and ELISA were used to determine TREM-1 expressions and cytokines release by monocytes. RESULTS: P. gingivalis LPS can induce a significant increase in TREM-1 expression (mRNA, membrane-bound and soluble form, p < 0.001) as well as cytokines (IL-1β, TNFα) and chemokines (IL-8) production by monocytes. This monocytes' activation was partly prevented by LR12. CONCLUSIONS: TREM-1 inhibitors such as LR12 could be interesting for the modulation of the excessive inflammatory response that occurs during periodontal disease.
Authors: Yrna Lorena Matos de Oliveira; Ayane de Sá Resende; Paulo Ricardo Martins-Filho; Tatiana Rodrigues de Moura Journal: Inflammopharmacology Date: 2022-03-28 Impact factor: 4.473