title: Type I and type II interferons inhibit both basal and tumor necrosis factor-α-induced CXCL8 secretion in primary cultures of human thyrocytes.
abstract: Interferons (IFNs) and tumor necrosis factor-α (TNF-α) cooperate in activating several inflammation-related genes, which sustain chronic inflammation in autoimmune thyroid disease (AITD). Much is known about the positive signaling of IFNs to activate gene expression in AITD, while the mechanisms by which IFNs negatively regulate genes remain less studied. While IFNs inhibit CXCL8 secretion in several human cell types, their effects on thyroid cells were not evaluated. Our aim was to study the interplay between TNF-α and type I or type II IFNs on CXCL8 secretion by human thyroid cells. CXCL8 was measured in supernatants of primary cultures of thyroid cells basally and after a 24-h incubation with TNF-α. CXCL8 was detected in thyroid cell supernatants in basal conditions (96.2±23.5 pg/mL) being significantly increased (784.7±217.3 pg/mL; P<0.0001 vs. basal) by TNF-α. Twenty-four hour incubation with IFN-γ or IFN-β or IFN-α dose dependently and significantly inhibited both basal and TNF-α-induced CXCL8 secretion. The degree of the inhibitory effect was IFN-γ>IFN-β>IFN-α. This study demonstrates that type I and type II IFNs downregulate both basal and TNF-α-induced CXCL8 secretion by human thyrocytes, IFN-γ being the most powerful inhibitor. Future studies aimed at a better comprehension of the interplay between CXCL8 and thyroid diseases appear worthwhile.
authors.affiliation: Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri I.R.C.C.S., University of Pavia, Pavia, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Rotondi
authors.forename: Francesca
authors.initials: F
authors.lastname: Coperchini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sideri
authors.forename: Gloria
authors.initials: G
authors.lastname: Groppelli
authors.forename: Luca
authors.initials: L
authors.lastname: de Martinis
authors.forename: Laura
authors.initials: L
authors.lastname: Villani
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pignatti
authors.forename: Flavia
authors.initials: F
authors.lastname: Magri
authors.forename: Luca
authors.initials: L
authors.lastname: Chiovato
mesh_terms: D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D006111:Graves Disease / Q000097:blood / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism*; D061251:Primary Cell Culture; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007370:Interferon Type I; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma