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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Dermatophagoides / immunology
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Antigens, Dermatophagoides / pharmacology*
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Arthropod Proteins / immunology
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Arthropod Proteins / pharmacology*
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Bronchi / cytology
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Bronchi / drug effects
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Bronchi / immunology
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Cell Line
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Cytokines / antagonists & inhibitors*
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Cytokines / biosynthesis
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Dose-Response Relationship, Drug
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Epithelial Cells / cytology
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Epithelial Cells / drug effects*
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Epithelial Cells / immunology
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Gene Expression / drug effects*
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Humans
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I-kappa B Kinase / genetics
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I-kappa B Kinase / immunology
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MAP Kinase Kinase 4 / antagonists & inhibitors
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MAP Kinase Kinase 4 / genetics
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MAP Kinase Kinase 4 / immunology
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Mites / chemistry
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / immunology
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / immunology
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NF-kappa B / agonists
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NF-kappa B / genetics
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NF-kappa B / immunology
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Perilla frutescens / chemistry*
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Plant Extracts / isolation & purification
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Plant Extracts / pharmacology*
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Plant Leaves / chemistry*
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Signal Transduction
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / genetics
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p38 Mitogen-Activated Protein Kinases / immunology
Substances
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Antigens, Dermatophagoides
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Arthropod Proteins
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Cytokines
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Dermatophagoides pteronyssinus antigen p 2
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NF-kappa B
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Plant Extracts
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I-kappa B Kinase
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
Grants and funding
This work was supported by grants from the National Science Council (NSC99-2320-B040-003-MY3, NSC99-2632-B040-001-MY3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.