Targeting a cysteine protease from a pathobiont alleviates experimental arthritis

doi:10.1186/s13075-020-02205-z

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24858

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/24858

Title:	Targeting a cysteine protease from a pathobiont alleviates experimental arthritis
Authors:	Peng, HY;Chen, SY;Siao, SH;Chang, JT;Xue, TY;Lee, YH;Jan, MSO;Tsay, GJ;Zouali, M
Keywords:	Rheumatoid arthritis;Periodontitis;Porphyromonas gingivalis;Gingipain;Collagen-induced arthritis
Date:	2020
Issue Date:	2022-08-09T08:09:08Z (UTC)
Publisher:	BMC
ISSN:	1478-6354
Abstract:	Background Several lines of evidence suggest that the pathobiont Porphyromonas gingivalis is involved in the development and/or progression of auto-inflammatory diseases. This bacterium produces cysteine proteases, such as gingipain RgpA, endowed with the potential to induce significant bone loss in model systems and in patients. Objective We sought to gain further insight into the role of this pathobiont in rheumatoid arthritis (RA) and to identify novel therapeutic targets for auto-inflammatory diseases. Methods We profiled the antibody response to RgPA-specific domains in patient sera. We also tested the potential protective effects of RgpA domains in an experimental arthritis model. Results Pre-immunization of rats with purified recombinant RgpA domains alleviated arthritis in the joints of the rodents and reduced bone erosion. Using a functional genomics approach at both the mRNA and protein levels, we report that the pre-immunizations reduced arthritis severity by impacting a matrix metalloprotease characteristic of articular injury, a chemokine known to be involved in recruiting inflammatory cells, and three inflammatory cytokines. Finally, we identified an amino acid motif in the RgpA catalytic domain of P. gingivalis that shares sequence homology with type II collagen. Conclusion We conclude that pre-immunization against gingipain domains can reduce the severity of experimentally induced arthritis. We suggest that targeting gingipain domains by pre-immunization, or, possibly, by small-molecule inhibitors, could reduce the potential of P. gingivalis to translocate to remote tissues and instigate and/or exacerbate pathology in RA, but also in other chronic inflammatory diseases.
URI:	http://dx.doi.org/10.1186/s13075-020-02205-z https://www.webofscience.com/wos/woscc/full-record/WOS:000536097200001 https://ir.csmu.edu.tw:8080/handle/310902500/24858
Relation:	ARTHRITIS RESEARCH & THERAPY ,2020 ,v22 ,issue 1
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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