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• W2035701076 abstract "Propionibacterium acnes (P. acnes), a gram-positive anaerobic bacterium, plays a critical role in the development of inflammatory lesion as a result of cytokines production by keratinocytes and macrophages activation. However, effect of P. acnes on iNOS/NO and COX-2/PGE2 production in macrophages is still uninvestigated.This study aimed at determining the reactive oxygen species (ROS), inducible nitric oxide (NO) synthase (iNOS)/nitric oxide (NO), and cyclooxygenase (COX)-2/prostaglandin (PG)E2 produced by macrophages upon P. acnes infection, and dissecting the mechanism of P. acnes-stimulated multiplicity of infection (MOI)-dependent increases in iNOS and COX-2 protein expressions in accordance with the elevation of NO and PGE2 production by RAW264.7 macrophages.Using an in vitro cell culture system, the effects of P. acnes on iNOS/NO, COX-2/PGE2, ROS production, ERK/JNK, and AP-1/NF-κB activation were examined via Western blotting, a flow cytometric analysis, and luciferase assay. In pharmacological studies, the ROS scavenger, N-acetyl cysteine (NAC), the NADPH oxidase inhibitor, diphenylene iodide (DPI), and mitogen-activated protein kinase (MAPK) inhibitors (U0126 and SP600125) were applied to investigate the mechanism.We found that P. acnes exposures increased iNOS/NO and COX-2/PGE2 expression in RAW264.7, J774A.1, and peritoneal macrophages via a MOI-dependent manner. Increased ROS production, ERK/JNK protein phosphorylation, and elevated AP-1/NF-κB luciferase activity are identified in P. acnes-induced iNOS/NO and COX-2/PGE2 production. Additionally, hispolon but not its analogs, hispolon methylether or dehydroxyhispolon, showed significant inhibition of P. acnes-induced iNOS/NO and COX-2/PGE2 production, indicating an important role of OH at C5 for hispolon's inhibition of P. acnes-induced inflammatory events in macrophages.ROS-dependent stimulation of ERK, JNK, NF-κB, and AP-1 activation contributes to P. acnes-induced iNOS/NO and COX-2/PGE2 in macrophages, and chemicals such as hispolon possessing ability to block iNOS/NO and COX-2/PGE2 production reserve potential to be further developed for treatment of the early phase of inflammation elicited by P. acnes." @default.
• W2035701076 created "2016-06-24" @default.
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• W2035701076 date "2013-02-01" @default.
• W2035701076 modified "2023-10-17" @default.
• W2035701076 title "Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-κB and AP-1 activation in macrophages" @default.
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• W2035701076 doi "https://doi.org/10.1016/j.jdermsci.2012.10.009" @default.
• W2035701076 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23178030" @default.
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