Inflammatory cytokine regulation of TRAIL-mediated apoptosis in thyroid epithelial cells.
Death receptor-mediated apoptosis has been implicated in target organ destruction in chronic autoimmune thyroiditis. Depending on the circumstances, inflammatory cytokines such as IL-1, TNF and IFNgamma have been shown to contribute to either the induction, progression or inhibition of this disease. Here we demonstrate that the death ligand TRAIL can induce apoptosis in primary, normal, thyroid epithelial cells under physiologically relevant conditions, specifically, treatment with the combination of inflammatory cytokines IL-1beta and TNFalpha. In contrast, IFNgamma is capable of blocking TRAIL-induced apoptosis in these cells. This regulation of TRAIL-mediated apoptosis by inflammatory cytokines appears to be due to alterations of cell surface expression of TRAIL receptor DR5 and not DR4. We also show the in vivo presence of TRAIL and TRAIL receptors DR5 and DcR1 in both normal and inflamed thyroids. Our data suggests TRAIL-mediated apoptosis may contribute to target organ destruction in chronic autoimmune thyroiditis.
Bretz
J D
JD
Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Mezosi
E
E
Giordano
T J
TJ
Gauger
P G
PG
Thompson
N W
NW
Baker
J R
JR
D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D058851:GPI-Linked Proteins; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000378:metabolism; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; D013961:Thyroid Gland / Q000166:cytology; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; D058851:GPI-Linked Proteins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C108661:TNFRSF10C protein, human; C505653:TNFSF10 protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha