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

PLoS One. 2013 Oct 18;8(10):e77458. doi: 10.1371/journal.pone.0077458. eCollection 2013.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Dermatophagoides / immunology
  • Antigens, Dermatophagoides / pharmacology*
  • Arthropod Proteins / immunology
  • Arthropod Proteins / pharmacology*
  • Bronchi / cytology
  • Bronchi / drug effects
  • Bronchi / immunology
  • Cell Line
  • Cytokines / antagonists & inhibitors*
  • Cytokines / biosynthesis
  • Dose-Response Relationship, Drug
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / immunology
  • Gene Expression / drug effects*
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / immunology
  • MAP Kinase Kinase 4 / antagonists & inhibitors
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / immunology
  • Mites / chemistry
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / immunology
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / immunology
  • NF-kappa B / agonists
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Perilla frutescens / chemistry*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry*
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / immunology

Substances

  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Cytokines
  • Dermatophagoides pteronyssinus antigen p 2
  • NF-kappa B
  • Plant Extracts
  • I-kappa B Kinase
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • 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.