当前位置： SCI文献检索 > JOURNAL OF DERMATOLOGICAL SCIENCE期刊下所有文献 > Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-κB and AP-1 activation in macrophages.

Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-κB and AP-1 activation in macrophages.

Abstract：

BACKGROUND: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. OBJECTIVE: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. METHODS: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. RESULTS: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. CONCLUSION: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.

journal_name

J Dermatol Sci

journal_title

Journal of dermatological science

authors

Tsai HH,Lee WR,Wang PH,Cheng KT,Chen YC,Shen SC

doi

10.1016/j.jdermsci.2012.10.009

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

122-31

issue

eissn

0923-1811

issn

1873-569X

pii

S0923-1811(12)00319-2

journal_volume

pub_type

杂志文章

在线工具

Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-κB and AP-1 activation in macrophages.