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

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

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. H&E-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.

Highlights

Skin is the largest organ in the body, and is directly exposed to extrinsic assaults
In order to evaluate the anti-inflammatory effect of BrD1 on TPA-induced dermatitis in a murine model, we initially evaluated the possible inhibitory effect of BrD1 on TPA-induced vascular permeability
BrD1 inhibits TPA-induced edema Since increased vascular permeability is one of factors contributing to the formation of edema, we evaluated whether BrD1 inhibited formation of edema in TPA

Summary

Introduction

Skin is the largest organ in the body, and is directly exposed to extrinsic assaults. 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. Skin is the largest organ in the body. As the primary interface between the body and environment, it serves as the first line of defense against microbial pathogens as well as physical and chemical stress or insults [1,2]. The skin does serve as a physical and a chemical barrier, but is an immune-competent organ that elicits effective innate and adaptive immune responses to protect the human body. It is clear that inadequate or misdirected immune response is involved in the pathogenesis of a variety of acquired inflammatory skin disorders [1].

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