Background: Thyrocytes secrete CXC chemokines, particularly (C-X-C motif)ligand (CXCL)8 and CXCL10; its physiopathological significance remains unclear. This study investigates the modulation of the secretion of CXCL8 vs. CXCL10, in human primary cells cultures of thyroid follicular cells (TFC)in Graves' disease (GD), and fibroblasts (OF)or preadipocytes (OP)from Graves' ophthalmopathy (GO). Methods: Cells were initially incubated with different concentrations of tumor necrosis factor (TNF)α (1, 5, 10 ng/mL). Then, CXCL8 and CXCL10 were measured in the supernatants of TFC, OF or OP cells basally and after 24 h of treatment with interferon (IFN)γ (1000 IU/mL)and/or TNFα (10 ng/mL), in presence/absence of the peroxisome proliferator activated receptor (PPAR)γ agonist pioglitazone (0, 0.1, 1, 5, 10, 20 μM), or the PPARα agonist fenofibrate (5, 10, 50, 100 μM). Results: CXCL8, not CXCL10, was detected in basal conditions in TFC, OF and OP. CXCL8 secretion increased dose-dependently with increasing concentrations of TNFα. CXCL10 secretion was significantly stimulated by IFNγ (P < 0.01)and not by TNFα, whereas CXCL8 was induced by TNFα (P < 0.01), and inhibited by IFNγ (P < 0.01)in TFC, OF and OP. Combining TNFα and IFNγ, the IFNγ-induced CXCL10 secretion was synergistically increased (P < 0.01)while the TNFα-induced CXCL8 secretion (P < 0.01)was reversed in all cell types. Pioglitazone had no significant effect on the secretion of CXCL8 stimulated by TNFα, while inhibited CXCL10. Fenofibrate, in presence of IFNγ plus TNFα, dose-dependently inhibited both CXCL10 and CXCL8 release. Conclusion: We first show that TFC, OF, and OP secrete CXCL8 and CXCL10 differentially, sustained by specific proinflammatory cytokines or their combination. This could reflect a different role of the two chemokines in the course of the disease, as CXCL10 could be associated with the initial phase of the disease when IFNγ is preponderant, while CXCL8 could be associated with a later chronic phase of the disease, when TNFα prevails.

Differential modulation of CXCL8 versus CXCL10, by cytokines, PPAR-gamma, or PPAR-alpha agonists, in primary cells from Graves' disease and ophthalmopathy

Ferrari S. M.;Ragusa F.;Nardi M.;Franceschini S. S.;Fallahi P.;Antonelli A.
2019-01-01

Abstract

Background: Thyrocytes secrete CXC chemokines, particularly (C-X-C motif)ligand (CXCL)8 and CXCL10; its physiopathological significance remains unclear. This study investigates the modulation of the secretion of CXCL8 vs. CXCL10, in human primary cells cultures of thyroid follicular cells (TFC)in Graves' disease (GD), and fibroblasts (OF)or preadipocytes (OP)from Graves' ophthalmopathy (GO). Methods: Cells were initially incubated with different concentrations of tumor necrosis factor (TNF)α (1, 5, 10 ng/mL). Then, CXCL8 and CXCL10 were measured in the supernatants of TFC, OF or OP cells basally and after 24 h of treatment with interferon (IFN)γ (1000 IU/mL)and/or TNFα (10 ng/mL), in presence/absence of the peroxisome proliferator activated receptor (PPAR)γ agonist pioglitazone (0, 0.1, 1, 5, 10, 20 μM), or the PPARα agonist fenofibrate (5, 10, 50, 100 μM). Results: CXCL8, not CXCL10, was detected in basal conditions in TFC, OF and OP. CXCL8 secretion increased dose-dependently with increasing concentrations of TNFα. CXCL10 secretion was significantly stimulated by IFNγ (P < 0.01)and not by TNFα, whereas CXCL8 was induced by TNFα (P < 0.01), and inhibited by IFNγ (P < 0.01)in TFC, OF and OP. Combining TNFα and IFNγ, the IFNγ-induced CXCL10 secretion was synergistically increased (P < 0.01)while the TNFα-induced CXCL8 secretion (P < 0.01)was reversed in all cell types. Pioglitazone had no significant effect on the secretion of CXCL8 stimulated by TNFα, while inhibited CXCL10. Fenofibrate, in presence of IFNγ plus TNFα, dose-dependently inhibited both CXCL10 and CXCL8 release. Conclusion: We first show that TFC, OF, and OP secrete CXCL8 and CXCL10 differentially, sustained by specific proinflammatory cytokines or their combination. This could reflect a different role of the two chemokines in the course of the disease, as CXCL10 could be associated with the initial phase of the disease when IFNγ is preponderant, while CXCL8 could be associated with a later chronic phase of the disease, when TNFα prevails.
2019
Ferrari, S. M.; Ragusa, F.; Paparo, S. R.; Nasini, F.; Nardi, M.; Franceschini, S. S.; Fallahi, P.; Antonelli, A.
File in questo prodotto:
File Dimensione Formato  
Autoimmun Rev 2019 non def.pdf

solo utenti autorizzati

Descrizione: Article in press
Tipologia: Versione finale editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 575.04 kB
Formato Adobe PDF
575.04 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Autoimmun Rev 2019.pdf

Open Access dal 01/08/2020

Tipologia: Documento in Post-print
Licenza: Creative commons
Dimensione 1.22 MB
Formato Adobe PDF
1.22 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/992198
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 14
social impact