In conclusion, we demonstrated the clinical usefulness of surgical specimens for finding LP by using ��-synuclein immunohistochemistry. Detection of LP in GI and biliary surgical specimens may help us to support a clinical diagnosis of LBD. Our methodology does not require any invasive procedures for patients. Further analyses may enable early medical intervention in individuals with selleck screening library LBD. Acknowledgements This work was partly supported by Grants-in-Aid from the Research Committee of CNS Degenerative Diseases (H23-nanchi-ippan-015), Abnormal protein propagation (H25-Shinkei- Kin, Ippan-002), the Ministry of Health, Labor and Welfare of Japan, Kiban B (24300133), the Comprehensive Brain Science Network (221S003), the Ministry of Education, Culture, Sports, Science and Technology of Japan, and National Center for Geriatrics and Gerontology Fund (23-42), Obu, Japan.
The authors thank Dr. Kinuko Suzuki (Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology) for insightful comments and useful discussions, and Dr. Takeshi Iwatsubo (Department of Neuropathology, the University of Tokyo, Tokyo, Japan) for the kind gifts of antibodies. We also thank Mr. Naoo Aikyo, Ms. Mieko Harada, Ms. Yuuki Kimura, and Ms. Nobuko Naoi for technical help. Disclosure of conflict of interest We declare no conflict of interest.
Crohn’s disease (CD) and ulcerative colitis (UC), which develop as the result of chronic inflammatory reactions in the gastrointestinal tract and are defined collectively as inflammatory bowel disease (IBD), are among the most common autoimmune diseases worldwide [1]�C[4].
IBD results from the unregulated response of the mucosal immune system in the gut [5]. It is involved in autoimmune diseases and increases the risk of developing colorectal cancer, one of the most common fatal malignancies [6]. Despite recent advances in our understanding of IBD, important questions about the molecular mechanisms of its immunopathology remain unanswered. Immune cells, which infiltrate the inflamed guts of patients with IBD, produce various cytokines and chemokines that trigger inflammatory responses [5]. Among the cytokines, interleukin-6 (IL-6) has a positive correlation with the disease activities of IBD, and its production returns to normal levels when gut inflammation becomes inactive [7]�C[11]. Of important, IL-6 production was also increased in DSS-induced colitis [11]�C[14].
IL-6 plays an important role in enhancing T-cell survival and apoptosis resistance in the lamina propria at the inflamed site [13], [15]. It is also involved in the immune deviation of regulatory T cells toward inflammatory cells (e.g., Th17) [16] and promotes the survival of intestinal epithelial cells [14], [17]. In general, IL-6 binds to soluble or membrane-bound IL-6 receptors Batimastat (e.g.