Luteolin suppresses IL-31 production in IL-33-stimulated mast cells through MAPK and NF-κB signaling pathways

• Published in: International immunopharmacology Vol. 83; p. 106403
• Main Authors: Che, Denis Nchang, Shin, Jae Young, Kang, Hyun Ju, Cho, Byoung Ok, Kim, Young-Soo, Jang, Seon Il
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2020; Elsevier BV
• Subjects: Anti-Inflammatory Agents - therapeutic use; Apium; Binding sites; Brassica; Cell culture; Cell Degranulation; Cells, Cultured; Chemical compounds; Culture media; Cytokines; Deoxyribonucleic acid; Dietary Supplements; DNA; Enzyme-linked immunosorbent assay; Functional foods & nutraceuticals; Gene expression; HMC-1.2; Humans; IL-31; IL-33; Immunofluorescence; Interleukin-33 - metabolism; Interleukins - metabolism; Luteolin; Luteolin - therapeutic use; MAP kinase; MAPK; Mast cells; Mast Cells - immunology; Medical treatment; Mitogen-Activated Protein Kinase Kinases - metabolism; Natural products; NF-kappa B - metabolism; NF-κB; NF-κB protein; Nuclear transport; Onions; Pharmacology; Signal Transduction; Signaling; Translocation; NF-κB; Luteolin; MAPK; HMC-1.2; IL-33; IL-31
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106403

•IL-33 stimulates production of IL-31 in HMC-1 cells.•Luteolin suppresses mRNA expression and production of IL-31 in IL-33-stimulated HMC-1 cells.•Luteolin inhibits activation of MAPK and NF-κB in IL-33-stimulated HMC-1.•Luteolin inhibits NF-κB/p65 binding to its consensus DNA sequence in the nucleus. IL-31 and IL-33 are cytokines, which are expressed in many inflammatory and pathological disorders, thus suggesting an IL-31/IL-33 axis interaction in pathological diseases. Luteolin from natural products is known for its anti-inflammatory activities associated with the regulation of inflammatory signaling pathways. Here, we investigated the effects of luteolin in the regulation of IL-33-stimulated production and secretion of IL-31 in HMC-1.2 mast cells. Human mast cells (HMC-1.2) were treated with luteolin and stimulated with IL-33. Real-time PCR was used to measure IL-31 mRNA expression. Western blot and immunofluorescence assays were used to measure IL-31 expression. ELISA techniques were used to measure IL-31 secretion and NF-κB-DNA-binding activities. The results revealed that luteolin inhibited the expression of IL-31 in IL-33-stimulated HMC-1.2 cells at the mRNA and protein levels. Also, Luteolin inhibited the secretion of IL-31 into the cell culture media of the IL-33-stimulated HMC-1.2 cells. Further findings demonstrated that luteolin inhibited the activation of ERK, JNK, p38, and NF-κB p65 in the IL-33-stimulated HMC-1.2 cells. In addition, luteolin also prevented the nuclear translocation and binding of p65 to its DNA-binding site. Based on the results, luteolin may be considered as a potential therapeutic or functional food agent for the prevention and/or treatment of IL-31 and IL-33-related diseases.