Bicyclic eremophilane-type petasite sesquiterpenes potentiate peroxisome proliferator–activated receptor γ activator–mediated inhibition of dendritic cells. (16th July 2018)

• Record Type: Journal Article
• Authors: Arizmendi, Narcy; Hou, Chenjie; Guo, Fujiang; Li, Yiming; Kulka, Marianna
• Is Part Of: International journal of immunopathology and pharmacology. Volume 32:Mar./Dec.(2018)
• Publication Date: 2018-07-16
• Subjects: inflammation -- peroxisome proliferator–activated receptor gamma -- plant derivatives -- transcription factor; Immunopathology -- Periodicals; Pharmacology -- Periodicals; Inflammation -- Periodicals; 615.1
• DOI: 10.1177/2058738418787739
• Languages: English
• ISSNs: 0394-6320

Abstract

Dendritic cell (DC) activation induces expression of co-stimulatory surface molecules, as well as migration into secondary lymphoid organs, where they activate naïve T-cells. A family of plant derivatives, eremophilane-type petasite sesquiterpenes, can regulate the immune system through DC targeting due to their anti-inflammatory effects. Peroxisome proliferator–activated receptor gamma (PPARγ) is involved in inhibition of inflammatory responses and induction of DCs to acquire a mucosal phenotype. Since mucosal DCs are central in innate immune responses, we hypothesized that eremophilane-type petasite sesquiterpenes exerted their anti-inflammatory effects by inhibiting DC maturation and activation through PPARγ. This study assessed the bicyclic eremophilane-type petasite sesquiterpene compounds Fukinone and 10βH-8α, 12-Epidioxyeremophil-7(11)-en-8β-ol (ZYFDC21 and ZYFDC22) in the maturation and activation of mouse DC. We measured surface expression of co-stimulatory molecules by flow cytometry and cell-free supernatant cytokine production upon lipopolysaccharide stimulation by enzyme-linked immunosorbent assays (ELISAs) in the presence or absence of PPARγ agonists. DCs were generated from C57BL/6 mice bone marrow cells and harvested. Cells were exposed to bicyclic eremophilane-type petasite sesquiterpenes ZYFDC21 or ZYFDC22 in the presence or absence of synthetic PPARγ agonists (GW1929 and TGZ) or the natural PPARγ ligand 15d-PGJ2, followed by overnight activation with LPS. We observed differences in the upregulation of surface expression of CD86, along with TNF, IL-6, and IL-12p70 released by DCs stimulated with LPS, when using combinations of bicyclic eremophilane-type petasite sesquiterpenes ZYFDC21 or ZYFDC22, and PPARγ agonists, in particular the PPARγ ligand 15d-PGJ2 . Our results indicate that bicyclic eremophilane-type petasite sesquiterpenes ZYFDC21 or ZYFDC22 inhibit maturation and activation of DC, and this activity is augmented upon PPARγ activation.