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  • Title: Exploration of retinoid activity and the role of inflammation in acne: issues affecting future directions for acne therapy.
    Author: Zouboulis CC.
    Journal: J Eur Acad Dermatol Venereol; 2001; 15 Suppl 3():63-7. PubMed ID: 11843237.
    Abstract:
    The review summarizes new results concerned with several important issues in the treatment of patients with acne. The first section reviews studies which show that 13-cis retinoic acid, a molecule with strong biological activity but low binding affinity for retinoid receptors and cellular-binding proteins in sebocytes, undergoes rapid intracellular conversion to all-trans retinoic acid. This active metabolite exerts its actions on sebocyte gene expression by binding to the nuclear retinoic acid receptor rather than the retinoid X receptor. Importantly, 13-cis retinoic acid, unlike all-trans retinoic acid, does not induce cytochrome P450 1A1, an enzyme responsible for the metabolism of xenobiotics. Thus, administration of 13-cis retinoic acid permits high long-term intracellular accumulation of its active metabolite. The second section reviews studies which suggest that leukotriene B4 may play a key role in acne-related inflammation. Results from a preliminary clinical study indicate that therapy with a specific lipoxygenase inhibitor is clinically effective in the treatment of patients with inflammatory acne and that its clinical efficacy is correlated with the drug's ability to reduce total lipid levels, and especially pro-inflammatory lipids, in sebum. Interestingly, 13-cis retinoic acid has been shown to modulate the activities of LTB4 and inflammatory events in the development of acne. Therefore, future compounds targeting acne have to inhibit pro-inflammatory lipids in sebum, and thus down-regulate acne-related inflammatory signals and reduce the LTB4-induced migration of inflammatory cells.
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