Wogonin ameliorates the proliferation, inflammatory response, and pyroptosis in keratinocytes via NOD‐like receptor family pyrin domain containing 3/Caspase‐1/Gasdermin‐D pathway

• Published in: Immunity, Inflammation and Disease Vol. 12; no. 7; pp. e1303 - n/a
• Main Authors: Ma, Jun, Ji, Chen, Sun, Yanhong, Liu, Danqing, Pan, Kai, Wei, Yuegang
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.07.2024; John Wiley and Sons Inc; Wiley
• Subjects: Caspase 1 - metabolism; Cell growth; Cell Line; Cell Proliferation - drug effects; Chemokines; Chinese medicine; Cytokines; Flavanones - pharmacology; Gasdermins; HaCaT Cells; Herbal medicine; Humans; Inflammation - drug therapy; Inflammation - metabolism; inflammatory response; Intracellular Signaling Peptides and Proteins - metabolism; Ischemia; Keratin; Keratinocytes - drug effects; Keratinocytes - metabolism; Ligands; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NOD‐like receptor family pyrin domain containing 3/Caspase‐1/Gasdermin‐D pathway; Original; Phosphate-Binding Proteins; Proteins; Psoriasis; Psoriasis - drug therapy; Psoriasis - metabolism; Psoriasis - pathology; pyroptosis; Pyroptosis - drug effects; Reagents; Signal Transduction - drug effects; Software; Tumor necrosis factor-TNF; Wogonin; inflammatory response; pyroptosis; NOD‐like receptor family pyrin domain containing 3/Caspase‐1/Gasdermin‐D pathway; Wogonin; psoriasis
• DOI: 10.1002/iid3.1303
• ISSN: 2050-4527

Background Psoriasis refers to a highly prevalent and immunologically mediated dermatosis with considerable deterioration in life quality. Wogonin, a sort of flavonoid, has been mentioned to elicit protective activities in skin diseases. However, whether Wogonin is implicated in the treatment of psoriasis and its specific mechanisms are not fully understood. Aim The present work attempted to elaborate the role of Wogonin during the process of psoriasis and to concentrate on the associated action mechanism. Methods Cell counting kit‐8 (CCK‐8) method was initially applied to assay the viability of human keratinocyte HaCaT cells treated by varying concentrations of Wogonin. To mimic psoriasis in vitro, HaCaT cells were exposed to M5 cytokines. CCK‐8 and 5‐Ethynyl‐2′‐deoxyuridine  assays were adopted for the measurement of cell proliferation. Inflammatory levels were examined with enzyme‐linked immunosorbent assay. Immunofluorescence staining tested nucleotide‐binding oligomerization domain (NOD)‐like receptor family pyrin domain containing 3 (NLRP3) and Caspase‐1 expressions. Western blot examined the protein expressions of proliferation‐, inflammation‐, pyroptosis‐associated factors, and NLRP3. Results Wogonin treatment antagonized the proliferation, inflammatory response, and NLRP3/caspase‐1/Gasdermin‐D (GSDMD)‐mediated pyroptosis in M5‐challenged HaCaT cells. Besides, NLRP3 elevation partially abrogated the effects of Wogonin on M5‐induced proliferation, inflammatory response, and NLRP3/caspase‐1/GSDMD‐mediated pyroptosis in HaCaT cells. Conclusion In a word, Wogonin might exert anti‐proliferation, anti‐inflammatory and anti‐pyroptosis activities in M5‐induced cell model of psoriasis and the blockade of NLRP3/Caspase‐1/GSDMD pathway might be recognized as a potential mechanism underlying the protective mechanism of Wogonin in psoriasis, suggesting Wogonin as a prospective anti‐psoriasis drug. Wogonin was capable of alleviating the hyperproliferation, inflammatory response as well as pyroptosis in HaCaT keratinocytes exposed to M5 cytokines, the effects of which might be related to the blockade of NOD‐like receptor family pyrin domain containing 3/Caspase‐1/Gasdermin‐D  pathway.