Jin-Kyung Kim1, Geun-Mook Park. 1. Department of Biomedical Science, College of Natural Science, Catholic University of Daegu, 330 Geumrak-Ri, Gyeoungsan-Si 700-712, Korea. toto0818@cu.ac.kr
Abstract
OBJECTIVE: Indirubin-3-monoxime (I3M), an indirubin analogue that shows favorable inhibitory activity targeting cyclin-dependent kinase and glycogen synthase kinase, exhibits various biological properties, including chemopreventive, antiangiogenic, and neuropreventive activities. In the present study, we investigated the ability of I3M to regulate inflammatory reactions in macrophages. METHODS: The effects of I3M on inflammation, lipopolysaccharide (LPS)-induced releases of inflammatory mediators, nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling was examined by ELISA and Western blotting analysis. RESULTS: I3M suppressed not only the generation of nitric oxide (NO) and prostaglandin E(2) but also the expression of inducible NO synthase and cyclooxygenase-2 induced by LPS. Similarly, I3M inhibited the release of pro-inflammatory cytokines induced by LPS in RAW264.7 cells, including interleukin (IL)-1β and IL-6. The underlying mechanism of I3M on anti-inflammatory action was correlated with down-regulation of the NF-κB and MAPK activation. CONCLUSIONS: Our data collectively indicate that I3M inhibited the production of several inflammatory mediators and might be used for the treatment of various inflammatory diseases.
OBJECTIVE:Indirubin-3-monoxime (I3M), an indirubin analogue that shows favorable inhibitory activity targeting cyclin-dependent kinase and glycogen synthase kinase, exhibits various biological properties, including chemopreventive, antiangiogenic, and neuropreventive activities. In the present study, we investigated the ability of I3M to regulate inflammatory reactions in macrophages. METHODS: The effects of I3M on inflammation, lipopolysaccharide (LPS)-induced releases of inflammatory mediators, nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling was examined by ELISA and Western blotting analysis. RESULTS: I3M suppressed not only the generation of nitric oxide (NO) and prostaglandin E(2) but also the expression of inducible NO synthase and cyclooxygenase-2 induced by LPS. Similarly, I3M inhibited the release of pro-inflammatory cytokines induced by LPS in RAW264.7 cells, including interleukin (IL)-1β and IL-6. The underlying mechanism of I3M on anti-inflammatory action was correlated with down-regulation of the NF-κB and MAPK activation. CONCLUSIONS: Our data collectively indicate that I3M inhibited the production of several inflammatory mediators and might be used for the treatment of various inflammatory diseases.
Authors: Roger Yazbeck; Ruth Lindsay; Catherine A Abbott; Kirsten Benkendorff; Gordon S Howarth Journal: Evid Based Complement Alternat Med Date: 2015-05-13 Impact factor: 2.629
Authors: Tina Blazevic; Anja M Schaible; Katharina Weinhäupl; Daniel Schachner; Felix Nikels; Christina Weinigel; Dagmar Barz; Atanas G Atanasov; Carlo Pergola; Oliver Werz; Verena M Dirsch; Elke H Heiss Journal: Cardiovasc Res Date: 2013-12-23 Impact factor: 10.787