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Statins inhibit chemotactic interaction between CCL20 and CCR6 in vitro : possible relevance to psoriasis treatment

Other Titles
 CCL20과 CCR6의 상호작용에서 스타틴의 억제 효과에 대한 연구 
 Dept. of Microbiology (미생물학교실) 
Issue Date
Dept. of Medicine/석사
Psoriasis is a common and chronic inflammatory skin disease which is associated with IL-23/Th17 pathway. An increased expression of CC chemokine ligand 20 (CCL20) in psoriatic lesions can attract CC chemokine receptor 6 (CCR6)-expressing Th17 cells into the lesions. Lipid-lowering drugs, statins, possess other immune-modulating functions. We explored whether specific types of statins could inhibit CCL20 production in HaCaT cells. We also investigated whether statins could attenuate the chemotactic migration of CD4+ T cells toward CCL20.We used enzyme-linked immunosorbent assay to evaluate CCL20 release from HaCaT cells stimulated by psoriasis-associated cytokines with or without statins. We performed fluorescence-activated cell sorting to investigate the level of surface CCR6 and CD45RO expression on human CD4+ T cells in various conditions. Functionally, the in vitro chemotaxis migration assay was performed and the number of migrating cells was analyzed using a flow cytometry.We demonstrated that IL-1β, TNF-α, and IL-17A significantly increased CCL20 production from HaCaT cells in a dose-dependent manner. However, these increments were significantly inhibited by the addition of fluvastatin and simvastatin, but not by pravastatin. In the in vitro chemotaxis migration assay, pretreatment with fluvastatin and simvastatin, but not with pravastatin, inhibited the chemotactic migration of human CD4+ T cells toward CCL20. However the level of surface expression of CCR6 on CD4+ T cells was not altered by statins.Our results suggest that not all, but specific types of statins may be of benefit in managing psoriasis partially via interrupting the chemotactic interaction of CCL20/CCR6, the mechanism which eventually lessen the infiltration of lesional Th17 cells.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 2. Thesis
Yonsei Authors
Kim, Tae-Gyun(김태균) ORCID logo https://orcid.org/0000-0002-2116-4579
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