Affiliation:
1. College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28160, Republic of Korea
2. D. Nature Co., Ltd., Seongnam 13174, Republic of Korea
Abstract
Psoriasis, a chronic inflammation-mediated skin disease, affects 2–3% of the global population. It is characterized by keratinocyte hyperproliferation and immune cell infiltration. The JAK/STAT3 and JAK/STAT1 signaling pathways play an important role in the development of psoriasis when triggered by IL-6 and IFN-γ, which are produced by dendritic cells and T-lymphocytes. Thus, blocking JAK/STAT signaling may be a potential strategy for treating psoriasis. Therefore, we examined the effects of CMX, an extract of Centipeda minima enriched in Brevilin A, Arnicolide D, Arnicolide C, and Microhelenin C, on macrophages and keratinocytes. We established an in vitro model of psoriasis, based on an inflammation-associated keratinocyte proliferation model, and used macrophages and keratinocytes treated with LPS, IL-6, or IFN-γ to evaluate the effect of CMX. We found that CMX reduced pro-inflammatory cytokine production, by inhibiting lipopolysaccharide (LPS)-induced JAK1/2 and STAT1/3 phosphorylation in macrophages. Moreover, CMX-downregulated chemokine expression and cell proliferation compared with components in HaCaT cells, induced by rh-IL-6 and rh-IFN-γ, respectively. Consistently, we demonstrated that the reduction in chemokine expression and hyperproliferation was mediated by the regulation of IFN-γ-activated JAK/STAT1 and IL-6-activated JAK/STAT3 signaling. In conclusion, CMX inhibited JAK/STAT-mediated inflammatory responses and cell proliferation in macrophages and keratinocytes. Consequently, CMX may have potential uses as a therapeutic agent for treating psoriasis.
Funder
National Research Foundation of Korea
Korean Food and Drug Administration
Regional Innovation Strategy grant from the Ministry of Education, South Korea
academic research program of Chungbuk National University
Subject
Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science
Cited by
2 articles.
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