Early chemokine expression induced by interferon-gamma in a murine model of Hashimoto's thyroiditis.
Chemokines represent a group of small, secreted proteins mainly involved in navigating leukocytes towards site of inflammation. Some chemokines have been implicated in the pathogenesis of autoimmune diseases, which are characterized by an ectopic retention of leukocytes within the target organ, ultimately leading to loss of function. To determine the chemokines profile expressed in the thyroid gland upon chronic exposure to interferon-gamma (IFNgamma), we analyzed C57BL6 transgenic mice that aberrantly express IFNgamma under control of the thyroglobulin promoter. We compared by reverse transcriptase PCR the thyroidal expression of 10 chemokines (CCL1 through 5 and CXCL9 through 13) in thyr-IFNgamma transgenics and wild-type littermates. We found that transgenics exclusively expressed CCL4, CXCL9, and CXCL11, and showed increased expression of CCL5 and CXCL10. This chemokine profile was associated with moderate mononuclear cell infiltration of the thyroid stroma that, however, decreased significantly after 2 months of age and did not organize into lymphoid structures. Our findings indicate that the isolated expression of IFNgamma is capable of recruiting mononuclear cells but they do not progress to full lymphoid transformation of the thyroid.
Kimura
Hiroaki
H
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Kimura
Miho
M
Rose
Noel R
NR
Caturegli
Patrizio
P
D000818:Animals; D018925:Chemokines / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
D018925:Chemokines; D012333:RNA, Messenger; D007371:Interferon-gamma