{"id":36274,"date":"2015-06-03T11:07:50","date_gmt":"2015-06-03T11:07:50","guid":{"rendered":"https:\/\/www.etap-lab.com\/?p=9853"},"modified":"2026-04-15T22:48:13","modified_gmt":"2026-04-15T20:48:13","slug":"shaping-mycolactone-for-therapeutic-use-against-inflammatory-disorders","status":"publish","type":"ressource","link":"https:\/\/www.etap-lab.com\/en\/ressource\/shaping-mycolactone-for-therapeutic-use-against-inflammatory-disorders\/","title":{"rendered":"Shaping mycolactone for therapeutic use against inflammatory disorders"},"content":{"rendered":"<p>Inflammation adversely affects the health of millions of people worldwide, and there is an unmet medical need for better anti-<span class=\"high-light\">inflammatory<\/span>&nbsp;drugs. We evaluated the&nbsp;<span class=\"high-light\">therapeutic<\/span>&nbsp;interest of&nbsp;<span class=\"high-light\">mycolactone<\/span>, a polyketide-derived macrolide produced by Mycobacterium ulcerans. Bacterial production of<span class=\"high-light\">mycolactone<\/span>&nbsp;in human skin causes a combination of ulcerative, analgesic, and anti-<span class=\"high-light\">inflammatory<\/span>&nbsp;effects. Whereas ulcer formation is mediated by the proapoptotic activity of&nbsp;<span class=\"high-light\">mycolactone<\/span>&nbsp;on skin cells via hyperactivation of Wiskott-Aldrich syndrome proteins, analgesia results from neuronal hyperpolarization via signaling through angiotensin II type 2 receptors.&nbsp;<span class=\"high-light\">Mycolactone<\/span>&nbsp;also blunts the capacity of immune cells to produce<span class=\"high-light\">inflammatory<\/span>&nbsp;mediators by an independent mechanism of protein synthesis blockade. In an attempt to isolate the structural determinants of<span class=\"high-light\">mycolactone<\/span>&#8216;s immunosuppressive activity, we screened a library of synthetic subunits of&nbsp;<span class=\"high-light\">mycolactone<\/span>&nbsp;for inhibition of cytokine production by activated T cells. The minimal structure retaining immunosuppressive activity was a truncated version of&nbsp;<span class=\"high-light\">mycolactone<\/span>, missing one of the two core-branched polyketide chains. This compound inhibited the&nbsp;<span class=\"high-light\">inflammatory<\/span>&nbsp;cytokine responses of human primary cells at noncytotoxic doses and bound to angiotensin II type 2 receptors comparably to&nbsp;<span class=\"high-light\">mycolactone<\/span>&nbsp;in vitro. Notably, it was considerably less toxic than&nbsp;<span class=\"high-light\">mycolactone<\/span>&nbsp;in human primary dermal fibroblasts modeling ulcerative activity. In mouse models of human diseases, it conferred systemic protection&nbsp;<span class=\"high-light\">against<\/span>&nbsp;chronic skin inflammation and&nbsp;<span class=\"high-light\">inflammatory<\/span>&nbsp;pain, with no apparent side effects. In addition to establishing the anti-<span class=\"high-light\">inflammatory<\/span>&nbsp;potency of&nbsp;<span class=\"high-light\">mycolactone<\/span>&nbsp;in vivo, our study therefore highlights the translational potential of&nbsp;<span class=\"high-light\">mycolactone<\/span>&nbsp;core-derived structures as prospective immunosuppressants.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Discover Shaping mycolactone for therapeutic use against inflammatory disorders: Inflammation adversely affects the health of millions of people worldwide, and there is an unmet medical\u2026<\/p>\n","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false},"categorie-de-ressource":[235],"marque-de-ressource":[],"class_list":["post-36274","ressource","type-ressource","status-publish","hentry","categorie-de-ressource-publications"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Shaping mycolactone for therapeutic use against inflammatory disorders - 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