Published online before print October 17, 2006
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results in less fibrosis and earlier resolution of granulomatous experimental autoimmune thyroiditis
,
Departments of *Internal Medicine, Pathology, and Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, Missouri, USA; and VA Research Service, Columbia, Missouri, USA
@ To whom correspondence should be addressed. E-mail: chenk{at}health.missouri.edu.
Granulomatous experimental autoimmune thyroiditis (G-EAT) is induced in DBA/1 mice by adoptive transfer of mouse thyroglobulin (MTg)-primed spleen cells. TNF-
is an important proinflammatory cytokine and apoptotic molecule involved in many autoimmune diseases. To study its role in G-EAT, anti-TNF- mAb was given to recipient mice. Disease severity was comparable between mice with or without anti-TNF- treatment at days 19-21, the time of maximal severity of G-EAT, suggesting TNF- is not essential for development of thyroid inflammation. However, thyroid lesions resolved at day 48 in anti-TNF--treated mice, while thyroids of rat Ig-treated controls had fibrosis. These results suggested that reducing TNF- 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--treated controls had reduced proinflammatory and profibrotic molecules, e.g., IFN-
, IL-1
, 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--treated mice. The site of expression of the anti-apoptotic molecule FLIP also differed between rat Ig-treated and anti-TNF--treated mice. FLIP was predominantly expressed by inflammatory cells of rat Ig-treated mice and by thyrocytes of anti-TNF--treated mice. These results suggest that anti-TNF- may regulate expression of proinflammatory cytokines and apoptosis in thyroids, resulting in less inflammation, earlier resolution, and reduced fibrosis.
Key Words: rodent • autoimmunity • cytokines
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