Effects of Klebsiella pneumoniae on Toll-Like Receptor-Dependent Endoplasmic Reticulum Stress-Related Signaling Pathways and Gene Expression and Promotes HLA-B27 Misfolding  

作　　者：Wen-Jen Cheng Yu-Ling Wei James Cheng-Chung Wei Chia-Wei Lin Hui-Yin Lu Yu-Pu Hsia Pei-Jane Tsai Ying-Chun Lai Yu-Liang Kuo Ming-Shiou Jan 

机构地区：[1]Department of Emergency, Antai Tian-Sheng Memorial Hospital, Ping Tong 928, Taiwan, R.O.C. [2]Institute of Medicine, Chung Shan Medical University, Taiehung 402, Taiwan, R.O.C. [3]Graduate Institute of lntegrated Medicine, China Medical University, Taichung 404, Taiwan, R. O. C. [4]Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital Taichung 402, Taiwan, R.O.C. [5]Institute of Biochemistry, Microbiology and lmmunology, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C. [6]Department of Biomedical Sciences, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C. [7]Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan, R.O.C. [8]School of Applied Foreign Languages, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C. [9]Department of Medical lmaging, Chung Shan Medical University Hospital, Taichung 402, Taiwan, R.O.C. [10]School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C. [11]Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C.

出　　处：《Journal of Pharmacy and Pharmacology》2016年第12期667-678,共12页药剂与药理学（英文版）

摘　　要：Klebsiella has been considered as initiator of AS （ankylosing spondylitis） for nearly four decades. This study aimed to demonstrate that Klebsiella triggers ERS （endoplasmic reticulum stress） and HLA-B27 heavy chain misfolding. CA46 cells or splenocytes obtained from wild-type, MyD88/ or TLR9/ mice were stimulated with KP （Klebsiella pneumoniae） or its components including CPS （capsule polysaccharide）, LPS （lipopolysaccharide）, and KP gDNA （genomic deoxyribonucleic acid） respectively for 24 h and 48 h. The activation of ERS-related signaling was detected by Western blotting or RT-PCR, and the level of misfolded HLA-B27 was determined by non-reducing protein gel electrophoresis and Western blotting. The protein expression of BiP/Grp78 and calreticulin, the alternative splicing of XBP-1 mRNA （messenger ribonucleic acid）, and the activation of caspase-12 and p38 were increased in a dose-dependent manner in HLA-B27-expressing CA46 cells after treatment with decapsulated KP. We also demonstrate that the EP, S-inducing effects occur via the TLR （Toll-like receptor）/MyD88-dependent signaling pathway. Significantly, HLA-B27 misfolding was also detected in decapsulated KP-treated B27-expressing cells. These results suggest that the non-antigen-specific induction of ERS and B27 misfoiding through TLR/MyD88 signaling might promote KP antigen-initiated autoreactive responses via the presentation of misfolded B27, and that small-molecules targeting TLRs might have potential as novel therapeutic agents for AS.

关 键 词：Klebsiella pneumoniae endoplasmic reticulum stress ankyiosing spondylitis Toll-like receptor 9 MYD88 HLA-B27misfolding. 

分 类 号：R[医药卫生]