LOX-1 is involved in IL-1β production and extracellular matrix breakdown in dental peri-implantitis

摘要

Abstract Purpose To explore whether lectin-type oxidized LDL receptor 1 (LOX-1), interleukin 1 beta (IL-1β), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) are involved in the nosogenesis of human dental peri-implantitis and determine the role of LOX-1 in IL-1β, MMP2 and MMP9 production in response to Porphyromonas gingivalis . Methods Peri-implant crevicular fluid (PICF) was collected from ten patients with healthy implants and ten patients with peri-implantitis. The LOX-1 protein in PICF was detected by Western-blot, and the expression of LOX-1 in superficial gingiva of peri-implantitis patients was detected by immunofluorescence staining. The IL-1β, MMP2 and MMP9 proteins in PICF were detected by enzyme-linked immunosorbent assay (ELISA). THP-1 macrophages were pretreated with neutralizing antibody (LOX-1) and inhibitors (LOX-1 and c-Jun N-terminal kinase, JNK) to evaluate the role of LOX-1 and JNK in IL-1β production, as well as the role of LOX-1 in MMP2 and MMP9 production in response to P . gingivalis by quantitative polymerase chain reaction (RT-PCR) and Western-blot. Results LOX-1, IL-1β, MMP2 and MMP9 increased in PICF of peri-implantitis patients and in THP-1 macrophages on P . gingivalis stimulation. IL-1β, MMP2 and MMP9 production in response to P . gingivalis in THP-1 macrophages was dependent on LOX-1. JNK was responsible for LOX-1 induced IL-1β production as a result of P . gingivalis infection. Conclusion LOX-1 is involved in IL-1β production and extracellular matrix breakdown is a novel inflammatory pathway trigger and potential drug target in human dental peri-implantitis. Highlights ? LOX-1, IL-1β, MMP2 and MMP9 are involved in human dental peri-implantitis. ? LOX-1 reduces P . gingivalis induced IL-1β production in macrophages. ? JNK was responsible for LOX-1 induced IL-1β production upon P . gingivalis infection. ? P . gingivalis induced MMP2 and MMP9 production in macrophages is dependent on LOX-1.