Osthole Inhibits Expression of Genes Associated with Toll-like Receptor 2 Signaling Pathway in an Organotypic 3D Skin Model of Human Epidermis with Atopic Dermatitis.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Gene Expression Regulation*/drug effects ; Models, Biological* ; Signal Transduction*/genetics; Coumarins/*pharmacology ; Dermatitis, Atopic/*genetics ; Dermatitis, Atopic/*pathology ; Epidermis/*pathology ; Toll-Like Receptor 2/*metabolism; Cells, Cultured ; Chemokines/metabolism ; Cyclooxygenase 2/metabolism ; Histamine/pharmacology ; Humans ; Inflammation/pathology ; Lipopolysaccharides/pharmacology ; Male ; Tight Junctions/drug effects ; Tight Junctions/metabolism

The Toll-like receptor (TLR) family signature has been linked to the etiopathology of atopic dermatitis (AD), a chronic inflammatory skin disease associated with skin barrier dysfunction and immune system imbalance. We aimed to investigate whether osthole (a plant-derived compound) can inhibit the genetic profile of key genes associated with TLR2 signaling ( TIRAP , MyD88 , IRAK1 , TRAF6 , IκBα , NFκB ) after stimulation with LPS or histamine in a 3D in vitro model of AD. Overexpression of the aforementioned genes may directly increase the secretion of proinflammatory cytokines (CKs) and chemokines (ChKs), which may exacerbate the symptoms of AD. Relative gene expressions were quantified by qPCR and secretion of CKs and ChKs was evaluated by ELISA assay. LPS and histamine increased the relative expression of genes related to the TLR2 pathway, and osthole successfully reduced it. In summary, our results show that osthole inhibits the expression of genes associated with the TLR signaling pathway in a skin model of AD. Moreover, the secretion of CKs and ChKs after treatment of AD with osthole in a 3D skin model in vitro suggests the potential of osthole as a novel compound for the treatment of AD.

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2019/03/X/NZ1/01159 National Science Centre, Poland

Keywords: TIR domain-containing adaptor protein; clobetasol propionate; fexofenadine; interleukin receptor-associated kinase; lipopolysaccharide; nuclear factor kappa B

0 (Chemokines)
0 (Coumarins)
0 (Lipopolysaccharides)
0 (Toll-Like Receptor 2)
820484N8I3 (Histamine)
EC 1.14.99.1 (Cyclooxygenase 2)
XH1TI1759C (osthol)

Date Created: 20220111 Date Completed: 20220302 Latest Revision: 20220302

20250114

PMC8750192

10.3390/cells11010088

35011650