β (CCL2) and α (CXCL10) chemokine modulations by cytokines and peroxisome proliferator-activated receptor-α agonists in Graves' ophthalmopathy

No data are present in the literature about the effect of cytokines on the prototype beta chemokine (C-C motif) ligand 2 (CCL2) or of peroxisome proliferator-activated receptor alpha (PPAR alpha (PPARA)) activation on CCL2 and CXCL10 chemokines secretion in fibroblasts or preadipocytes in Graves' ophthalmopathy (GO). We have tested the effect of interferon gamma (IFN gamma (IFNG)) and tumor necrosis factor alpha (TNF alpha) on CCL2, and for comparison on the prototype alpha chemokine (C-X-C motif) ligand 10 (CXCL10), and the possible modulatory role of PPAR alpha activation on secretion of these chemokines in normal and GO fibroblasts or preadipocytes in primary cell cultures. This study shows that IFN gamma alone, or in combination with TNF alpha, stimulates the secretion of CCL2 in primary orbital fibroblasts or preadipocytes from patients with GO at levels similar to those observed in controls. IFN gamma and TNF alpha also stimulated CXCL10 chemokine secretion as expected. The presence of PPAR alpha and PPAR gamma (PPARG) in primary fibroblasts or preadipocytes of patients with GO has been confirmed. PPAR alpha activators were able to inhibit the secretion of CXCL10 and CCL2, while PPAR gamma activators were confirmed to be able to inhibit CXCL10 but had no effect on CCL2. PPAR alpha activators were stronger inhibitors of chemokine secretions than PPAR gamma agonists. In conclusion, CCL2 and CXCL10 are modulated by IFN gamma and TNF alpha in GO. PPAR alpha activators inhibit the secretion of the main prototype alpha (CXCL10) and beta (CCL2) chemokines in GO fibroblasts or preadipocytes, suggesting that PPAR alpha may be involved in the modulation of the immune response in GO. Journal of Endocrinology (2012) 213, 183-191