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TPA-induced dermatitis is thus a useful <jats:italic>in vivo<\/jats:italic> pharmacological platform for drug discovery. In this study, the inhibitory effect of briarane-type diterpenes (BrDs) from marine coral <jats:italic>Briareum excavatum<\/jats:italic> on TPA-induced dermatitis and dendritic cell (DC) function was explored.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Evans blue dye exudation was used to determine vascular permeability. H&amp;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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>BrD1 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-\u03baB-mediated signaling network. BrD1 also inhibited TNF-\u03b1 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our results suggest that BrDs warrant further investigation as natural immunomodulatory agents for control of inflammatory skin diseases.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1423-0127-18-94","type":"journal-article","created":{"date-parts":[[2011,12,21]],"date-time":"2011-12-21T19:18:50Z","timestamp":1324495130000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Topical application of marine briarane-type diterpenes effectively inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and dermatitis in murine skin"],"prefix":"10.1186","volume":"18","author":[{"given":"Wen-Chi","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Yen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Jyun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chun","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiung-Yao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arulselvan","family":"Palanisamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning-Sun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyh-Horng","family":"Sheu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,12,21]]},"reference":[{"key":"346_CR1","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nri1310","volume":"4","author":"TS Kupper","year":"2004","unstructured":"Kupper TS, Fuhlbrigge RC: Immune surveillance in the skin: mechanisms and clinical consequences. 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