Variable modulation by cytokines and thiazolidinediones of the prototype Th1 chemokine CXCL10 in anaplastic thyroid cancer.
Until now, no data are present in literature about the prototype Th1 chemokine (C-X-C motif) ligand 10 (CXCL10) in anaplastic thyroid cancer (ATC). This study aimed to test in "primary human ATC cells" (ANA) vs "normal thyroid follicular cells" (TFC): (a) CXCL10 secretion basally and after interferon (IFN)-γ and/or tumor necrosis factor (TNF)-α stimulation; (b) peroxisome proliferator-activated receptor (PPAR)-γ activation by thiazolidinediones, rosiglitazone or pioglitazone, on CXCL10 secretion, on proliferation and apoptosis in ANA. We demonstrate that: (a) ANA, but not TFC, produced basally CXCL10, and did so in half of cases; (b) IFN-γ stimulated dose-dependently CXCL10, in ANA and TFC; (c) TNF-α did not induce CXCL10 secretion, in ANA and TFC; (d) IFN-γ+TNF-α induced a synergistic but variable release of CXCL10 in the different ANA preparations, while it was more reproducible in TFC; (e) rosiglitazone action on CXCL10 in ANA was inhibitory in 2/6, stimulatory in 1/6 and nil in 3/6, whereas it was inhibitory in TFC; (f) rosiglitazone inhibition of proliferation in ANA was not associated with the effect on CXCL10; (g) nuclear factor-κB and ERK1/2 were basally activated in ANA, increased by IFN-γ+TNF-α, and rosiglitazone inhibited that activation. On the whole, the present data first show that ANA cells are able to produce CXCL10, basally and under the influence of cytokines. However, the pattern of modulation by IFN-γ, TNF-α or thiazolidinediones is extremely variable, suggesting that the intracellular pathways involved in the chemokine modulation in ATC have different types of deregulation.
Department of Internal Medicine, University of Pisa - School of Medicine, Via Roma 67, 56126 Pisa, Italy. alessandro.antonelli@med.unipi.it
Alessandro
A
Antonelli
Silvia Martina
SM
Ferrari
Poupak
P
Fallahi
Simona
S
Piaggi
Andrea
A
Di Domenicantonio
David
D
Galleri
Libero
L
Santarpia
Fulvio
F
Basolo
Ele
E
Ferrannini
Paolo
P
Miccoli
D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D015151:Immunoblotting; D000077154:Rosiglitazone; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*; D065646:Thyroid Carcinoma, Anaplastic; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D016207:Cytokines; D045162:Thiazolidinediones; D000077154:Rosiglitazone