Topical application of marine briarane-type diterpenes effectively inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and dermatitis in murine skinReportar como inadecuado




Topical application of marine briarane-type diterpenes effectively inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and dermatitis in murine skin - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Biomedical Science

, 18:94

First Online: 21 December 2011Received: 17 November 2011Accepted: 21 December 2011DOI: 10.1186-1423-0127-18-94

Cite this article as: Wei, WC., Lin, SY., Chen, YJ. et al. J Biomed Sci 2011 18: 94. doi:10.1186-1423-0127-18-94

Abstract

BackgroundSkin is the largest organ in the body, and is directly exposed to extrinsic assaults. As such, the skin plays a central role in host defense and the cutaneous immune system is able to elicit specific local inflammatory and systemic immune responses against harmful stimuli. 12-O-tetradecanoylphorbol-13-acetate TPA can stimulate acute and chronic inflammation and tumor promotion in skin. TPA-induced dermatitis is thus a useful in vivo pharmacological platform for drug discovery. In this study, the inhibitory effect of briarane-type diterpenes BrDs from marine coral Briareum excavatum on TPA-induced dermatitis and dendritic cell DC function was explored.

MethodsEvans blue dye exudation was used to determine vascular permeability. HandE-stained skin section was used to determine the formation of edema in mouse abdominal skin. We also used immunohistochemistry staining and western blot assays to evaluate the activation of specific inflammation makers and key mediators of signaling pathway in the mouse skin. Furthermore, mouse bone marrow DCs were used to determine the relationship between the chemical structure of BrDs and their regulation of DC function.

ResultsBrD1 remarkably suppressed TPA-induced vascular permeability and edema in skin. At the biochemical level, BrD1 inhibited TPA-induced expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase-9, the key indicators of cutaneous inflammation. This inhibition was apparently mediated by interference with the Akt-NF-κB-mediated signaling network. BrD1 also inhibited TNF-α and IL-6 expression in LPS-stimulated BMDCs. The 8, 17-epoxide of BrDs played a crucial role in the inhibition of IL-6 expression, and replacement of the C-12 hydroxyl group with longer esters in BrDs gradually decreased this inhibitory activity.

ConclusionsOur results suggest that BrDs warrant further investigation as natural immunomodulatory agents for control of inflammatory skin diseases.

KeywordsBriarane-type diterpene TPA-induced mouse dermatitis Dendritic cells Vascular permeability Edema Electronic supplementary materialThe online version of this article doi:10.1186-1423-0127-18-94 contains supplementary material, which is available to authorized users.

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Autor: Wen-Chi Wei - Sheng-Yen Lin - Yi-Jyun Chen - Chih-Chun Wen - Chiung-Yao Huang - Arulselvan Palanisamy - Ning-Sun Yang - Jyh

Fuente: https://link.springer.com/







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