Melatonin inhibits Prevotella intermedia lipopolysaccharide‐induced production of nitric oxide and interleukin‐6 in murine macrophages by suppressing NF‐κB and STAT1 activity

Abstract

Although a range of biological and pharmacological activities of melatonin have been reported, little is known about its potential anti-inflammatory efficacy in periodontal disease. In this study, we investigated the effects of melatonin on the production of inflammatory mediators by murine macrophages stimulated with lipopolysaccharide (LPS) from Prevotella intermedia, a major cause of inflammatory reactions in the periodontium, and sought to determine the underlying mechanisms of action. Melatonin suppressed the production of nitric oxide (NO) and interleukin-6 (IL-6) at both gene transcription and translation levels in P. intermedia LPS-activated RAW264.7 cells. P. intermedia LPS-induced NF-κB-dependent luciferase activity was significantly inhibited by melatonin. Melatonin did not reduce NF-κB transcriptional activity at the level of IκB-α degradation. Melatonin blocked NF-κB signaling through the inhibition of nuclear translocation and DNA-binding activity of NF-κB p50 subunit and suppressed STAT1 signaling. Although further research is required to clarify the detailed mechanism of action, we conclude that melatonin may contribute to blockade of the host-destructive processes mediated by these two proinflammatory mediators and could be a highly efficient modulator of host response in the treatment of inflammatory periodontal disease.

Melatonin and ubiquitin: what’s the connection?

“…Melatonin reduces nf-κB binding in spleen [89]. a number of laboratories report melatonin-induced inhibition of nK-κB activity or inhibition of nf-κB activation [90][91][92][93][94][95][96][97][98][99][100]. these results suggest an interaction of melatonin and the ubiquitin-proteasome system in the activation of nf-κB.…”

Gene regulation by melatonin linked to epigenetic phenomena

“…Hence it scavenges the ROS and RNS both directly and enzymatically. While fulfilling a dual antioxidant role, melatonin also blocks proinflammatory genes by interfering with the genomic binding of NF-κB (Choi et al, 2011;Chuang et al, 1996;Kang et al, 2011;Natarajan et al, 1995). These features strongly suggest that melatonin would be an ideal add-on therapeutic agent for the treatment of a variety of diseases including type 2 diabetes, hypertension, metabolic syndrome, and neurodegenerative diseases, all of which are related to free radicals as well as low to a moderate level of inflammation (Korkmaz et al, , 2009aReiter et al, 2009a;Rosales-Corral et al, 2010;Tan et al, 2011).…”

Effects of β-Glucan on the Release of Nitric Oxide by Macrophages Stimulated with Lipopolysaccharide

“…After the incubation, the supernatant was removed and dimethyl sulfoxide was added to dissolve the cells, and the absorbance of the formed formazan was measured at a wavelength of 570 nm using a Spectra Max 250 ELISA Reader (Molecular Devices, Sunnyvale, CA, USA). The cell viability was evaluated in percentage by comparing it with the control group (Choi et al, 2011). …”

“…After preparing the nuclear extracts from the cells as described above, the DNA-binding activities of NF-κB p65 or p50 in the nuclear extracts were quantified using the ELISA-based NF-κB transcription factor assay kit (Active Motif) according to the manufacturer’s instructions (Choi et al, 2011). …”