Paper Status Tracking

Article
Author(s)

Wen-Jen Cheng1, Yu-Ling Wei2, James Cheng-Chung Wei2, 3, 4, Chia-Wei Lin5, Hui-Yin Lu6, Yu-Pu Hsia6, Pei-Jane Tsai7, Ying­Chun Lai8, Yu-Liang Kuo9, 10 and Ming-Shiou Jan4, 5, 11

Affiliation(s)

1. Department of Emergency, Antai Tian-Sheng Memorial Hospital, Ping Tong 928, Taiwan, R.O.C.
2. Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C.
3. Graduate Institute of Integrated 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 Immunology, 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 Imaging, 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.

ABSTRACT

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 ERS-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 misfolding 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.

KEYWORDS

Klebsiella pneumoniae, endoplasmic reticulum stress, ankylosing spondylitis, Toll-like receptor 9, MyD88, HLA-B27 misfolding.

Cite this paper

References

About | Terms & Conditions | Issue | Privacy | Contact us
Coryright © 2015 David Publishing Company All rights reserved, 3 Germay Dr., Unit 4 #4651, Wilmington DE 19804
Tel: 1-323-984-7526, 323-410-1082; Fax: 1-323-984-7374, 323-908-0457 , www.davidpublisher.com, Email: order@davidpublishing.com