Topical application of Pseudolaric acid B improve DNFB-induced contact hypersensitivity via regulating the balance of Th1/Th17/Treg cell subsets.

Abstract

Pseudolaric acid B (PAB) is a novel diterpenoid, isolated from Pseudolarix kaempferi Gorden, which roots are widely used to treat inflammatory and microbial skin diseases for centuries, but the underlying mechanism remains elusive. To address the immunoregulatory mechanisms of PAB, we first investigated the effect of PAB in 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity (CHS) mice. The expression of specific transcription factors for T-helper (Th)1, Th2, Th17 and regulatory T cells (Tregs) was determined by RT-PCR, and the capacities for PAB to modulate Th1/Th17/Treg cell subsets was furtherly analyzed by flow cytometric analysis, ELISA and Western blotting assay. The results showed that topical application of PAB could suppress ear swelling, block inflammatory infiltration, and interfere in Th1 response. Furthermore, PAB-treated CHS mice exhibited the impaired Th17 development and enhanced Tregs generation, associated with the up-regulation of peroxisome proliferator activated-receptor γ (PPAR γ) expression. These findings suggest that PAB exerts its immunoregulatory activity through regulating the balance of Th1/Th17/Treg cell subsets, which would provide a novel therapeutic application for PAB on CHS and other inflammatory-associated diseases.

• Authors: Tan Li, Hong Chen, Zhen Yang, Na Wei, Shi Zhang, Xin Mei, Shu-Fang Bai
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 45 Issue 5 Pg. 668-76 (Apr 11 2012) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 22266211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Diterpenes
• Interleukin-6
• PPAR gamma
• STAT3 Transcription Factor
• Stat3 protein, mouse
• Transcription Factors
• pseudolaric acid B
• Dinitrofluorobenzene

Topics

• Administration, Topical
• Animals
• Dermatitis, Contact (drug therapy, immunology, metabolism)
• Dinitrofluorobenzene (immunology)
• Diterpenes (pharmacology)
• Female
• Immunomodulation (drug effects, genetics, immunology)
• Inflammation (drug therapy, genetics, immunology, metabolism)
• Interleukin-6 (immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• PPAR gamma (genetics, immunology, metabolism)
• STAT3 Transcription Factor (immunology, metabolism)
• Skin (drug effects, immunology, metabolism)
• T-Lymphocytes, Regulatory (drug effects, immunology, metabolism)
• Th1 Cells (drug effects, immunology, metabolism)
• Th17 Cells (drug effects, immunology, metabolism)
• Transcription Factors (genetics, metabolism)
• Up-Regulation (drug effects, genetics, immunology)