气候变化领域集成服务门户(CCPortal): 14-3-3ζ: A suppressor of inflammatory arthritis

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DOI	10.1073/pnas.2025257118
	14-3-3ζ: A suppressor of inflammatory arthritis
	Kim J.; Chun K.; McGowan J.; Zhang Y.; Czernik P.J.; Mell B.; Joe B.; Chattopadhyay S.; Holoshitz J.; Chakravarti R.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:34
英文摘要	Inflammatory arthritis (IA) is a common disease that affects millions of individuals worldwide. Proinflammatory events during IA pathogenesis are well studied; however, loss of protective immunity remains underexplored. Earlier, we reported that 14-3-3zeta (ζ) has a role in T-cell polarization and interleukin (IL)-17A signal transduction. Here, we demonstrate that 14-3-3ζ knockout (KO) rats develop early-onset severe arthritis in two independent models of IA, pristane-induced arthritis and collagen-induced arthritis. Arthritic 14-3-3ζ KO animals showed an increase in bone loss and immune cell infiltration in synovial joints. Induction of arthritis coincided with the loss of anti-14-3-3ζ antibodies; however, rescue experiments to supplement the 14-3-3ζ antibody by passive immunization did not suppress arthritis. Instead, 14-3-3ζ immunization during the presymptomatic phase resulted in significant suppression of arthritis in both wild-type and 14-3-3ζ KO animals. Mechanistically, 14-3-3ζ KO rats exhibited elevated inflammatory gene signatures at the messenger RNA and protein levels, particularly for IL-1β. Furthermore, the immunization with recombinant 14-3-3ζ protein suppressed IL-1β levels, significantly increased anti-14-3-3ζ antibody levels and collagen production, and preserved bone quality. The 14-3-3ζ protein increased collagen expression in primary rat mesenchymal cells. Together, our findings indicate that 14-3-3ζ causes immune suppression and extracellular remodeling, which lead to a previously unrecognized IA-suppressive function. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	14-3-3zeta; Bone loss; Collagen; Il-1beta; Inflammatory arthritis
语种	英语
scopus关键词	antibody; collagen; Freund adjuvant; messenger RNA; pristane; protein 14 3 3; terpene; animal; arthritis; bone density; bone disease; drug effect; female; gene deletion; gene expression regulation; genetics; immunology; inflammation; male; mesenchymal stem cell; metabolism; passive immunization; rat; 14-3-3 Proteins; Animals; Antibodies; Arthritis; Bone Density; Bone Diseases; Collagen; Female; Freund's Adjuvant; Gene Deletion; Gene Expression Regulation; Immunization, Passive; Inflammation; Male; Mesenchymal Stem Cells; Rats; RNA, Messenger; Terpenes
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251046
作者单位	Department of Physiology and Pharmacology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, United States; Department of Medical Microbiology and Immunology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, United States; Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, United States
推荐引用方式 GB/T 7714	Kim J.,Chun K.,McGowan J.,et al. 14-3-3ζ: A suppressor of inflammatory arthritis[J],2021,118(34).
APA	Kim J..,Chun K..,McGowan J..,Zhang Y..,Czernik P.J..,...&Chakravarti R..(2021).14-3-3ζ: A suppressor of inflammatory arthritis.Proceedings of the National Academy of Sciences of the United States of America,118(34).
MLA	Kim J.,et al."14-3-3ζ: A suppressor of inflammatory arthritis".Proceedings of the National Academy of Sciences of the United States of America 118.34(2021).