Abstract |
Autoimmune hypophysitis (AH) is an autoimmune disease of the pituitary for which the pathogenesis is incompletely known. AH is often treated with corticosteroids; however, steroids may lead to considerable side effects. Using a mouse model of AH (experimental autoimmune hypophysitis, EAH), we show that interleukin-1 receptor-associated kinase 1 (IRAK1) is upregulated in the pituitaries of mice that developed EAH. We identified rosoxacin as a specific inhibitor for IRAK1 and found it could treat EAH. Rosoxacin treatment at an early stage (day 0-13) slightly reduced disease severity, whereas treatment at a later stage (day 14-27) significantly suppressed EAH. Further investigation indicated rosoxacin reduced production of autoantigen-specific antibodies. Rosoxacin downregulated production of cytokines and chemokines that may dampen T cell differentiation or recruitment to the pituitary. Finally, rosoxacin downregulated class II major histocompatibility complex expression on antigen-presenting cells that may lead to impaired activation of autoantigen-specific T cells. These data suggest that IRAK1 may play a pathogenic role in AH and that rosoxacin may be an effective drug for AH and other inflammatory diseases involving IRAK1 dysregulation.
|
Authors | Hsiao-Chen Huang, Yun-Ti Chen, Han-Huei Lin, Zhi-Qin Li, Jinn-Moon Yang, Shey-Cherng Tzou |
Journal | International journal of molecular sciences
(Int J Mol Sci)
Vol. 23
Issue 23
(Nov 29 2022)
ISSN: 1422-0067 [Electronic] Switzerland |
PMID | 36499283
(Publication Type: Journal Article)
|
Chemical References |
- Autoantigens
- Interleukin-1 Receptor-Associated Kinases
- Irak1 protein, mouse
|
Topics |
- Autoantigens
- Autoimmune Hypophysitis
(therapy)
- Interleukin-1 Receptor-Associated Kinases
(antagonists & inhibitors)
- Animals
- Mice
|