IκB kinase (IKK) α exhibits diverse biological activities through protein kinase-dependent and -independent functions, the former mediated predominantly through a noncanonical NF-κB activation pathway. The in vivo function of IKKα, however, still remains elusive. Because a natural strain of mice with mutant NF-κB-inducing kinase (NIK) manifests autoimmunity as a result of disorganized thymic structure with abnormal expression of Rel proteins in the thymic stroma, we speculated that the NIK-IKKα axis might constitute an essential step in the thymic organogenesis that is required for the establishment of self-tolerance. An autoimmune disease phenotype was induced in athymic nude mice by grafting embryonic thymus from IKKα-deficient mice. The thymic microenvironment that caused autoimmunity in an IKKα-dependent manner was associated with defective processing of NF-κB2, resulting in the impaired development of thymic epithelial cells. Thus, our results demonstrate a novel function for IKKα in thymic organogenesis for the establishment of central tolerance that depends on its protein kinase activity in cooperation with NIK.
Pseudo-Meigs' syndrome secondary to uterine leiomyoma is a rare entity. A 50-year-old Japanese woman presented with a 3-month history of shortness of breath. Chest X-ray and magnetic resonance imaging revealed massive right pleural effusion, ascites and a large subserosal uterine myoma. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The pathology was consistent with a benign leiomyoma. The ascites and pleural effusion rapidly disappeared postoperatively. The serum interleukin-6 level was 3.9 pg/mL before surgery and declined to 1.6 pg/mL postoperatively. Previous published work has demonstrated that vascular endothelial growth factor and interleukin-6 may play a role in the pathogenesis of Meigs' syndrome and that vascular endothelial growth factor may contribute to the development of pseudo-Meigs' syndrome due to metastatic ovarian cancer. This is the first English-language study showing the possibility that interleukin-6 is relevant to the pathogenesis of pseudo-Meigs' syndrome caused by degenerating uterine leiomyoma.
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