Peroxisome proliferator-activated receptor-α agonists modulate CXCL9 and CXCL11 chemokines in Graves' ophthalmopathy fibroblasts and preadipocytes

Alessandro Antonelli; Silvia Martina Ferrari; Silvia Frascerra; Ilaria Ruffilli; Stefania Gelmini; Michele Minuto; Cinzia Pupilli; Paolo Miccoli; Stefano Sellari-Franceschini; Ele Ferrannini; Poupak Fallahi

doi:10.1016/j.mce.2011.11.001

Peroxisome proliferator-activated receptor-α agonists modulate CXCL9 and CXCL11 chemokines in Graves' ophthalmopathy fibroblasts and preadipocytes

Mol Cell Endocrinol. 2012 Feb 26;349(2):255-61. doi: 10.1016/j.mce.2011.11.001. Epub 2011 Nov 12.

Authors

Alessandro Antonelli¹, Silvia Martina Ferrari, Silvia Frascerra, Ilaria Ruffilli, Stefania Gelmini, Michele Minuto, Cinzia Pupilli, Paolo Miccoli, Stefano Sellari-Franceschini, Ele Ferrannini, Poupak Fallahi

Affiliation

¹ Department of Internal Medicine, University of Pisa - School of Medicine, Via Roma 67, I-56100 Pisa, Italy. [email protected]

PMID: 22101320
DOI: 10.1016/j.mce.2011.11.001

Abstract

Peroxisome proliferator-activated receptors (PPAR)α have been shown to exert immunomodulatory effects in autoimmune disorders; no study evaluated the effect of PPARα activation in Graves' ophthalmopathy (GO). We show the presence of PPARα, δ and γ in GO fibroblasts and preadipocytes. PPARα activators have a potent inhibitory action on the secretion of CXCL9 and CXCL11 chemokines (induced by IFNγ and TNFα) in fibroblasts and preadipocytes. The potency of the used PPARα agonists was maximum on the secretion of CXCL11 (67% inhibition by fenofibrate) in fibroblasts. The relative potency of the compounds in GO fibroblasts was different with each chemokine. PPARα agonists were stronger inhibitors of CXCL9 and CXCL11 (in GO fibroblasts and preadipocytes) than PPARγ activators. This study first shows that PPARα activators inhibit CXCL9 and CXCL11 chemokines in normal and GO fibroblasts and preadipocytes, suggesting that PPARα may be involved in the modulation of the immune response in GO.

MeSH terms

Adipocytes / drug effects
Adipocytes / immunology
Adipocytes / metabolism*
Adipocytes / pathology
Chemokine CXCL11 / antagonists & inhibitors
Chemokine CXCL11 / biosynthesis*
Chemokine CXCL11 / immunology
Chemokine CXCL9 / antagonists & inhibitors
Chemokine CXCL9 / biosynthesis*
Chemokine CXCL9 / immunology
Enzyme-Linked Immunosorbent Assay
Eye / immunology
Eye / metabolism
Eye / pathology
Fenofibrate / pharmacology
Fibroblasts / drug effects
Fibroblasts / immunology
Fibroblasts / metabolism*
Fibroblasts / pathology
Graves Ophthalmopathy / immunology
Graves Ophthalmopathy / metabolism*
Graves Ophthalmopathy / pathology
Humans
Hypolipidemic Agents / pharmacology
Interferon-gamma / pharmacology
PPAR alpha / agonists*
PPAR alpha / immunology
PPAR alpha / metabolism
PPAR delta / metabolism
PPAR gamma / metabolism
Primary Cell Culture
Signal Transduction
Thyroid Gland / immunology
Thyroid Gland / metabolism
Thyroid Gland / pathology
Tumor Necrosis Factor-alpha / pharmacology

Substances

CXCL11 protein, human
CXCL9 protein, human
Chemokine CXCL11
Chemokine CXCL9
Hypolipidemic Agents
PPAR alpha
PPAR delta
PPAR gamma
Tumor Necrosis Factor-alpha
Interferon-gamma
Fenofibrate