Identification and characterization of triamcinolone acetonide, a microglial-activation inhibitor

• Published in: Immunopharmacology and immunotoxicology Vol. 34; no. 6; pp. 912 - 918
• Main Authors: Hong, Jinpyo, Kim, Bo-Kyong, Lim, Hyoungsub, Lee, Soojin, Lee, Sung Joong
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01-12-2012; Taylor & Francis
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Cell Death - drug effects; Cell Line, Transformed; Cell Line, Tumor; cytokine; Cytokines - metabolism; Gene Expression Regulation - drug effects; Glucocorticoids - pharmacology; Lipopolysaccharides - toxicity; Mice; microglia; Microglia - metabolism; Microglia - pathology; necrotic neuronal cells; neuronal cell death; Neurons - metabolism; Neurons - pathology; NF-kappa B - metabolism; nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - biosynthesis; Rats; Signal Transduction - drug effects; Triamcinolone - analogs & derivatives; Triamcinolone - pharmacology; Triamcinolone acetonide; Triamcinolone Acetonide - pharmacology
• ISSN: 0892-3973; 1532-2513
• DOI: 10.3109/08923973.2012.671332

Recent studies show that necrotic neuronal cells (NNC) activate microglia, thereby leading to neuronal cell death. This suggests that chemicals that inhibit microglia activation may be used as neuroprotective drugs. In this context, we screened a chemical library for inhibitors of microglia activation. Using a screening system based on a nitrite assay, we isolated two chemicals that inhibit nitric oxide (NO) release from activated microglia: triamcinolone acetonide (TA) and amcinonide. The half-maximal inhibitory concentrations (IC50) of TA and amcinonide for NO release inhibition were 1.78 nM and 3.38 nM, respectively. These chemicals also inhibited NNC-induced expression of the proinflammatory genes iNOS, TNF-α, and IL-1β in glial cells. A study based on a luciferase assay revealed that TA attenuated NNC-induced microglia activation by blocking the NF-κB signaling pathway. In addition, TA protected cortical neurons in coculture with microglia from LPS/IFN-γ-induced neuronal cell death. In conclusion, TA may inhibit microglia activation and may protect neuronal cells from death induced by microglial activation.