title: Decreasing TNF-alpha results in less fibrosis and earlier resolution of granulomatous experimental autoimmune thyroiditis.
abstract: Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced in DBA/1 mice by adoptive transfer of mouse thyroglobulin (MTg)-primed spleen cells. TNF-alpha is an important proinflammatory cytokine and apoptotic molecule involved in many autoimmune diseases. To study its role in G-EAT, anti-TNF-alpha mAb was given to recipient mice. Disease severity was comparable between mice with or without anti-TNF-alpha treatment at days 19-21, the time of maximal severity of G-EAT, suggesting TNF-alpha is not essential for development of thyroid inflammation. However, thyroid lesions resolved at day 48 in anti-TNF-alpha-treated mice, while thyroids of rat Ig-treated controls had fibrosis. These results suggested that reducing TNF-alpha contributed to resolution of inflammation and inhibited fibrosis. Gene and protein expression of inflammatory molecules was examined by RT-PCR and immunostaining, and apoptosis was detected using TUNEL staining and an apoptosis kit. Thyroids of anti-TNF-alpha-treated controls had reduced proinflammatory and profibrotic molecules, e.g., IFN-gamma, IL-1beta, IL-17, inducible NOS and MCP-1, at day 19 compared with thyroids of rat Ig-treated mice. There were more apoptotic thyrocytes in rat Ig-treated controls than in anti-TNF-alpha-treated mice. The site of expression of the anti-apoptotic molecule FLIP also differed between rat Ig-treated and anti-TNF-alpha-treated mice. FLIP was predominantly expressed by inflammatory cells of rat Ig-treated mice and by thyrocytes of anti-TNF-alpha-treated mice. These results suggest that anti-TNF-alpha may regulate expression of proinflammatory cytokines and apoptosis in thyroids, resulting in less inflammation, earlier resolution, and reduced fibrosis.
authors.affiliation: Dept. of Internal Medicine, University of Missouri, M306 Medical Sciences, One Hospital Dr., Columbia, MO 65212, USA. chenk@health.missouri.edu
authors.forename: Kemin
authors.initials: K
authors.lastname: Chen
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Wei
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Sharp
authors.forename: Helen
authors.initials: H
authors.lastname: Braley-Mullen
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000378:metabolism / Q000628:therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D013968:Thyroiditis, Subacute / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha