title: Perilla frutescens leaf extract inhibits mite major allergen Der p 2-induced gene expression of pro-allergic and pro-inflammatory cytokines in human bronchial epithelial cell BEAS-2B.
abstract: Perilla frutescens has been used in traditional medicine for respiratory diseases due to its anti-bacterial and anti-inflammatory activity. This study aimed to investigate effects of Perilla frutescens leaf extract (PFE) on expression of pro-allergic and pro-inflammatory cytokines in airway epithelial cells exposed to mite major allergen Der p 2 (DP2) and the underlying mechanisms. Our results showed that PFE up to 100 µg/mL had no cytotoxic effect on human bronchial epithelial cell BEAS-2B. Further investigations revealed that PFE dose-dependently diminished mRNA expression of pro-allergic cytokine IL-4, IL-5, IL-13 and GM-CSF, as well as pro-inflammatory cytokine IL-6, IL-8 and MCP-1 in BEAS-2B cells treated with DP2. In parallel to mRNA, the DP-2-elevated levels of the tested cytokines were decreased. Further investigation showed that DP2-indued phosphorylation of p38 MAPK (P38) and JNK, but not Erk1/2, was also suppressed by PFE. In addition, PFE elevated cytosolic IκBα level and decreased nuclear NF-κB level in DP2-stimulated BEAS-2B cells. Taken together, these findings revealed that PFE significantly diminished both mRNA expression and protein levels of pro-allergic and pro-inflammatory cytokines in response to DP2 through inhibition of P38/JNK and NK-κB activation. These findings suggest that PFE should be beneficial to alleviate both allergic and inflammatory responses on airway epithelium in response to aeroallergens.
authors.affiliation: Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan ; Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Jer-Yuh
authors.initials: JY
authors.lastname: Liu
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Lin
authors.forename: Shao-Hsuan
authors.initials: SH
authors.lastname: Kao
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000494:pharmacology*; D060829:Arthropod Proteins / Q000276:immunology / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000276:immunology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D008925:Mites / Q000737:chemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000819:agonists / Q000235:genetics / Q000276:immunology; D031344:Perilla frutescens / Q000737:chemistry*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D016207:Cytokines; C451163:Dermatophagoides pteronyssinus antigen p 2; D016328:NF-kappa B; D010936:Plant Extracts; D051550:I-kappa B Kinase; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4