title: Statins inhibit chemotactic interaction between CCL20 and CCR6 in vitro: possible relevance to psoriasis treatment.
abstract: Psoriasis is a chronic IL-23/Th17 pathway-associated skin disease. An increased expression of lesional CCL20 can recruit CCR6+ Th17, and lesional cytokine milieu persistently activates keratinocytes to produce CCL20. Lipid-lowering drugs, statins, are known to possess immune-modulating functions. In this study, we explored an inhibitory effect of statins on CCL20/CCR6 interaction. We demonstrated that IL-1β, TNF-α, and IL-17A significantly increased CCL20 production from HaCaT cells. However, these increments were markedly inhibited by fluvastatin and simvastatin, but not by pravastatin. In the chemotaxis migration assay, pretreatment with fluvastatin and simvastatin inhibited the migration of human CD4+ T cells towards CCL20. However, the level of CCR6 surface expression in memory CD4+ T cells was not affected. Our results suggest that not all, but specific types of statins may be of benefit in alleviating psoriasis partially via interrupting CCL20/CCR6 chemotactic interaction, the mechanism which may eventually lessen the infiltration of Th17 cells.
authors.forename: Tae-Gyun
authors.initials: TG
authors.lastname: Kim
authors.forename: Dashlkhumbe
authors.initials: D
authors.lastname: Byamba
authors.forename: Wen Hao
authors.initials: WH
authors.lastname: Wu
authors.forename: Min-Geol
authors.initials: MG
authors.lastname: Lee
mesh_terms: D002460:Cell Line; D002464:Cell Migration Inhibition / Q000187:drug effects / Q000276:immunology; D054418:Chemokine CCL20 / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D020381:Interleukin-17 / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D054399:Receptors, CCR6 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C508717:IL17A protein, human; D020381:Interleukin-17; D053583:Interleukin-1beta; D054399:Receptors, CCR6; D014409:Tumor Necrosis Factor-alpha