ArticleJournal of clinical immunology2013
Anti-citrullinated protein antibodies activated ERK1/2 and JNK mitogen-activated protein kinases via binding to surface-expressed citrullinated GRP78 on mononuclear cells.
Article in Journal of clinical immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
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- Decreased expression of circ-CCDC134 mediated by TNF-α in patients with rheumatoid arthritis affects T cell function via targeting protein phosphatase 2A.Arthritis research & therapy · 2026Article
- Roles of Immunity and Endogenous Retroelements in the Pathogenesis of Rheumatoid Arthritis and Treatment Strategies.Functional & integrative genomics · 2025Review
- The Differential Expressions and Associations of Intracellular and Extracellular GRP78/Bip with Disease Activity and Progression in Rheumatoid Arthritis.Bioengineering (Basel, Switzerland) · 2025Article
- Citrullinated peptides as drug candidates for rheumatoid arthritis.Frontiers in immunology · 2025Review
- The monocyte cell surface is a unique site of autoantigen generation in rheumatoid arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Six-Month Follow-Up of Periodontal Condition in Rheumatoid Arthritis and Ankylosing Spondylitis Arthritis Patients Undergoing Anti-Tumour Necrosis Factor-α Therapy.Journal of clinical medicine · 2024Article
- HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.Biomolecules · 2023Review
- Increased Expression of Long Noncoding RNA LOC100506314 in T cells from Patients with Nonsegmental Vitiligo and Its Contribution to Vitiligo Pathogenesis.Mediators of inflammation · 2023Article
- Pathogenic mechanisms involving the interplay between adipose tissue and auto-antibodies in rheumatoid arthritis.iScience · 2022Article
- Physiological Roles of the Autoantibodies to the 78-Kilodalton Glucose-Regulated Protein (GRP78) in Cancer and Autoimmune Diseases.Biomedicines · 2022Review
- Macrophage Dysfunction in Autoimmune Rheumatic Diseases and Atherosclerosis.International journal of molecular sciences · 2022Review
- The role of Sirt6 in osteoarthritis and its effect on macrophage polarization.Bioengineered · 2022Article
- Pharmacogenomics of Anti-TNF Treatment Response Marks a New Era of Tailored Rheumatoid Arthritis Therapy.International journal of molecular sciences · 2022Review
- Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells.International journal of molecular sciences · 2022Review
- Brain-Derived Neurotrophic Factor Suppressed Proinflammatory Cytokines Secretion and Enhanced MicroRNA(miR)-3168 Expression in Macrophages.International journal of molecular sciences · 2022Article
- Impact of Posttranslational Modification in Pathogenesis of Rheumatoid Arthritis: Focusing on Citrullination, Carbamylation, and Acetylation.International journal of molecular sciences · 2021Review
- Specific Increase in Joint Neutrophil Extracellular Traps and Its Relation to Interleukin 6 in Autoimmune Arthritis.International journal of molecular sciences · 2021Article
- The Expression of Non-Coding RNAs and Their Target Molecules in Rheumatoid Arthritis: A Molecular Basis for Rheumatoid Pathogenesis and Its Potential Clinical Applications.International journal of molecular sciences · 2021Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In a previous study, we found that anti-citrullinated protein antibodies (ACPAs) enhance nuclear factor (NF)-κB activity and tumor necrosis factor (TNF)-α production by normal human peripheral blood mononuclear cells (PBMCs) and U937 cells via binding to surface-expressed citrullinated glucose-regulated protein 78 (cit-GRP78). However, the downstream signaling pathways remain unclear after binding. In the present study, we firstly measured the effects of different kinase inhibitors on ACPA-mediated TNF-α production from normal PBMCs and monocytes. Then, the native and phosphorylated mitogen-activated protein kinases (MAPKs) were detected in ACPA-activated U937 cells by Western blotting. We also explored the role of the phosphoinositide 3-kinase (PI3K)-Akt pathway in activating IκB kinase alpha (IKK-α) in ACPA-stimulated U937 cells. Finally, we measured the amount of cit-GRP78 from PBMC membrane extracts in RA patients and controls. We found that MAPK and Akt inhibitors, but not PI3K inhibitor, remarkably suppressed ACPA-mediated TNF-α production. Interestingly, ACPAs selectively activated extracellular signal-regulated kinase 1/2 (ERK1/2) and c-jun N-terminal kinase (JNK), but not p38 MAPK, in U937 cells. This activation was suppressed by cit-GRP78, but not GRP78. The JNK activation further enhanced the phosphorylation of Akt and IKK-α. The expression of cit-GRP78 on cell membrane was higher in RA than normal PBMCs. Taken together; these results suggest that through binding to surface, over-expressed cit-GRP78 on RA PBMCs, ACPAs selectively activate ERK1/2 and JNK signaling pathways to enhance IKK-α phosphorylation, which leads to the activation of NF-κB and the production of TNF-α .
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