The acute phase reactant orosomucoid-2 directly promotes rheumatoid inflammation.


Journal

Experimental & molecular medicine
ISSN: 2092-6413
Titre abrégé: Exp Mol Med
Pays: United States
ID NLM: 9607880

Informations de publication

Date de publication:
01 Apr 2024
Historique:
received: 27 08 2023
accepted: 20 12 2023
revised: 04 12 2023
medline: 1 4 2024
pubmed: 1 4 2024
entrez: 31 3 2024
Statut: aheadofprint

Résumé

Acute phase proteins involved in chronic inflammatory diseases have not been systematically analyzed. Here, global proteome profiling of serum and urine revealed that orosomucoid-2 (ORM2), an acute phase reactant, was differentially expressed in rheumatoid arthritis (RA) patients and showed the highest fold change. Therefore, we questioned the extent to which ORM2, which is produced mainly in the liver, actively participates in rheumatoid inflammation. Surprisingly, ORM2 expression was upregulated in the synovial fluids and synovial membranes of RA patients. The major cell types producing ORM2 were synovial macrophages and fibroblast-like synoviocytes (FLSs) from RA patients. Recombinant ORM2 robustly increased IL-6, TNF-α, CXCL8 (IL-8), and CCL2 production by RA macrophages and FLSs via the NF-κB and p38 MAPK pathways. Interestingly, glycophorin C, a membrane protein for determining erythrocyte shape, was the receptor for ORM2. Intra-articular injection of ORM2 increased the severity of arthritis in mice and accelerated the infiltration of macrophages into the affected joints. Moreover, circulating ORM2 levels correlated with RA activity and radiographic progression. In conclusion, the acute phase protein ORM2 can directly increase the production of proinflammatory mediators and promote chronic arthritis in mice, suggesting that ORM2 could be a new therapeutic target for RA.

Identifiants

pubmed: 38556552
doi: 10.1038/s12276-024-01188-0
pii: 10.1038/s12276-024-01188-0
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : National Research Foundation of Korea (NRF)
ID : NRF-2015R1A3A2032927
Organisme : National Research Foundation of Korea (NRF)
ID : NRF-2021R1I1A2059487
Organisme : National Research Foundation of Korea (NRF)
ID : NRF-2019R1A2C2010897
Organisme : Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs)
ID : 21A0503L1

Informations de copyright

© 2024. The Author(s).

Références

Moshage, H. Cytokines and the hepatic acute phase response. J. Pathol. 181, 257–266 (1997).
pubmed: 9155709 doi: 10.1002/(SICI)1096-9896(199703)181:3<257::AID-PATH756>3.0.CO;2-U
Gabay, C. & Kushner, I. Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 340, 448–454 (1999).
pubmed: 9971870 doi: 10.1056/NEJM199902113400607
Hochepied, T., Berger, F. G., Baumann, H. & Libert, C. Alpha(1)-acid glycoprotein: an acute phase protein with inflammatory and immunomodulating properties. Cytokine Growth Factor Rev. 14, 25–34 (2003).
pubmed: 12485617 doi: 10.1016/S1359-6101(02)00054-0
Pepys, M. B. & Hirschfield, G. M. C-reactive protein: a critical update. J. Clin. Investig. 111, 1805–1812 (2003).
pubmed: 12813013 pmcid: 161431 doi: 10.1172/JCI200318921
Rodriguez, W. et al. Prevention and reversal of nephritis in MRL/lpr mice with a single injection of C-reactive protein. Arthritis Rheumatol. 54, 325–335 (2006).
doi: 10.1002/art.21556
Fang, Z. et al. C-reactive protein promotes the activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis. Front. Immunol. 11, 958 (2020).
pubmed: 32508836 pmcid: 7251027 doi: 10.3389/fimmu.2020.00958
Lee, J. Y. et al. Serum amyloid A proteins induce pathogenic Th17 cells and promote inflammatory disease. Cell 183, 2036–2039 (2020).
pubmed: 33357400 pmcid: 7891798 doi: 10.1016/j.cell.2020.12.008
Lee, M. S. et al. Serum amyloid A binding to formyl peptide receptor-like 1 induces synovial hyperplasia and angiogenesis. J. Immunol. 177, 5585–5594 (2006).
pubmed: 17015746 doi: 10.4049/jimmunol.177.8.5585
Rolla, S. et al. Acute-phase protein hemopexin is a negative regulator of Th17 response and experimental autoimmune encephalomyelitis development. J. Immunol. 191, 5451–5459 (2013).
pubmed: 24154625 doi: 10.4049/jimmunol.1203076
Firestein, G. S. & McInnes, I. B. Immunopathogenesis of rheumatoid arthritis. Immunity 46, 183–196 (2017).
pubmed: 28228278 pmcid: 5385708 doi: 10.1016/j.immuni.2017.02.006
Bartok, B. & Firestein, G. S. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol. Rev. 233, 233–255 (2010).
pubmed: 20193003 pmcid: 2913689 doi: 10.1111/j.0105-2896.2009.00859.x
Bottini, N. & Firestein, G. S. Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. Nat. Rev. Rheumatol. 9, 24–33 (2013).
pubmed: 23147896 doi: 10.1038/nrrheum.2012.190
Kang, M. J. et al. Urinary proteome profile predictive of disease activity in rheumatoid arthritis. J. Proteome Res. 13, 5206–5217 (2014).
pubmed: 25222917 doi: 10.1021/pr500467d
Liu, S. et al. Fibrinogen-like protein 1 is a novel biomarker for predicting disease activity and prognosis of rheumatoid arthritis. Front. Immunol. 11, 579228 (2020).
pubmed: 33123164 pmcid: 7574527 doi: 10.3389/fimmu.2020.579228
Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847–2849 (2016).
pubmed: 27207943 doi: 10.1093/bioinformatics/btw313
Aletaha, D. et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheumatol. 62, 2569–2581 (2010).
doi: 10.1002/art.27584
Prevoo, M. L. et al. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheumatol. 38, 44–48 (1995).
doi: 10.1002/art.1780380107
van der Heijde, D. How to read radiographs according to the Sharp/van der Heijde method. J. Rheumatol. 27, 261–263 (2000).
pubmed: 10648051
Giles, J. T., van der Heijde, D. M. & Bathon, J. M. Association of circulating adiponectin levels with progression of radiographic joint destruction in rheumatoid arthritis. Ann. Rheum. Dis. 70, 1562–1568 (2011).
pubmed: 21571734 doi: 10.1136/ard.2011.150813
Stark, C. et al. BioGRID: a general repository for interaction datasets. Nucleic Acids Res. 34, D535–D539 (2006).
pubmed: 16381927 doi: 10.1093/nar/gkj109
Keshava Prasad, T. S. et al. Human protein reference database-2009 update. Nucleic Acids Res. 37, D767–D772 (2009).
pubmed: 18988627 doi: 10.1093/nar/gkn892
Bovolenta, L. A., Acencio, M. L. & Lemke, N. HTRIdb: an open-access database for experimentally verified human transcriptional regulation interactions. BMC Genom. 13, 405 (2012).
doi: 10.1186/1471-2164-13-405
Orchard, S. et al. The MIntAct project-IntAct as a common curation platform for 11 molecular interaction databases. Nucleic Acids Res. 42, D358–D363 (2014).
pubmed: 24234451 doi: 10.1093/nar/gkt1115
Szklarczyk, D. et al. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 43, D447–D452 (2015).
pubmed: 25352553 doi: 10.1093/nar/gku1003
Staite, N. D. et al. Induction of an acute erosive monarticular arthritis in mice by interleukin-1 and methylated bovine serum albumin. Arthritis Rheum. 33, 253–260 (1990).
pubmed: 2306293 doi: 10.1002/art.1780330215
Choi, S. et al. Transcription factor NFAT5 promotes macrophage survival in rheumatoid arthritis. J. Clin. Investig. 127, 954–969 (2017).
pubmed: 28192374 pmcid: 5330733 doi: 10.1172/JCI87880
Falconer, J. et al. Review: synovial cell metabolism and chronic inflammation in rheumatoid arthritis. Arthritis Rheumatol. 70, 984–999 (2018).
pubmed: 29579371 pmcid: 6019623 doi: 10.1002/art.40504
O’Neill, L. A. Targeting signal transduction as a strategy to treat inflammatory diseases. Nat. Rev. Drug Discov. 5, 549–563 (2006).
pubmed: 16773072 doi: 10.1038/nrd2070
Chang, S., Reid, M. E., Conboy, J., Kan, Y. W. & Mohandas, N. Molecular characterization of erythrocyte glycophorin C variants. Blood 77, 644–648 (1991).
pubmed: 1991173 doi: 10.1182/blood.V77.3.644.644
Croft, A. P. et al. Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature 570, 246–251 (2019).
pubmed: 31142839 pmcid: 6690841 doi: 10.1038/s41586-019-1263-7
Bagchi, S., Fredriksson, R. & Wallen-Mackenzie, A. In Situ Proximity Ligation Assay (PLA). Methods Mol. Biol. 1318, 149–159 (2015).
pubmed: 26160573 doi: 10.1007/978-1-4939-2742-5_15
Brand, D. D., Latham, K. A. & Rosloniec, E. F. Collagen-induced arthritis. Nat. Protoc. 2, 1269–1275 (2007).
pubmed: 17546023 doi: 10.1038/nprot.2007.173
Yang, Y. H. & Hamilton, J. A. Dependence of interleukin-1-induced arthritis on granulocyte-macrophage colony-stimulating factor. Arthritis Rheumatol. 44, 111–119 (2001).
doi: 10.1002/1529-0131(200101)44:1<111::AID-ANR15>3.0.CO;2-1
Yoshimura, T. The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally? Cell. Mol. Immunol. 15, 335–345 (2018).
pubmed: 29375123 pmcid: 6052833 doi: 10.1038/cmi.2017.135
Phillipson, M. & Kubes, P. The neutrophil in vascular inflammation. Nat. Med. 17, 1381–1390 (2011).
pubmed: 22064428 pmcid: 7095830 doi: 10.1038/nm.2514
Sun, Y. et al. Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis of Adult-Onset Still’s Disease. Front. Immunol. 11, 2112 (2020).
pubmed: 33013889 pmcid: 7500098 doi: 10.3389/fimmu.2020.02112
Elpek, G. O. Orosomucoid in liver diseases. World J. Gastroenterol. 27, 7739–7747 (2021).
pubmed: 34963738 pmcid: 8661375 doi: 10.3748/wjg.v27.i45.7739
Liu, Q. et al. Proteomic profiling for plasma biomarkers of tuberculosis progression. Mol. Med. Rep. 18, 1551–1559 (2018).
pubmed: 29901122 pmcid: 6072192
Lobo, C. A., Rodriguez, M., Reid, M. & Lustigman, S. Glycophorin C is the receptor for the Plasmodium falciparum erythrocyte binding ligand PfEBP-2 (baebl). Blood 101, 4628–4631 (2003).
pubmed: 12576308 doi: 10.1182/blood-2002-10-3076
King, M. J. et al. Reactivity with erythroid and non-erythroid tissues of a murine monoclonal antibody to a synthetic peptide having amino acid sequence common to cytoplasmic domain of human glycophorins C and D. Br. J. Haematol. 89, 440–448 (1995).
pubmed: 7734343 doi: 10.1111/j.1365-2141.1995.tb08347.x
Colin, Y. et al. Isolation of cDNA clones and complete amino acid sequence of human erythrocyte glycophorin C. J. Biol. Chem. 261, 229–233 (1986).
pubmed: 2416746 doi: 10.1016/S0021-9258(17)42458-6
Micieli, J. A., Wang, D. & Denomme, G. A. Anti-glycophorin C induces mitochondrial membrane depolarization and a loss of extracellular regulated kinase 1/2 protein kinase activity that is prevented by pretreatment with cytochalasin D: implications for hemolytic disease of the fetus and newborn caused by anti-Ge3. Transfusion 50, 1761–1765 (2010).
pubmed: 20456692 doi: 10.1111/j.1537-2995.2010.02640.x
Janciauskiene, S. et al. The multifaceted effects of alpha1-antitrypsin on neutrophil functions. Front. Pharmacol. 9, 341 (2018).
pubmed: 29719508 pmcid: 5914301 doi: 10.3389/fphar.2018.00341
Luan, Y. Y. & Yao, Y. M. The clinical significance and potential role of C-reactive protein in chronic inflammatory and neurodegenerative diseases. Front. Immunol. 9, 1302 (2018).
pubmed: 29951057 pmcid: 6008573 doi: 10.3389/fimmu.2018.01302
Bertaggia, E. et al. Haptoglobin is required to prevent oxidative stress and muscle atrophy. PLoS One 9, e100745 (2014).
pubmed: 24959824 pmcid: 4069100 doi: 10.1371/journal.pone.0100745

Auteurs

Ki-Myo Kim (KM)

Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, South Korea.
Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Kang-Gu Lee (KG)

Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, South Korea.
Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Saseong Lee (S)

Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, South Korea.

Bong-Ki Hong (BK)

Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, South Korea.

Heejae Yun (H)

Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, South Korea.
Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Yune-Jung Park (YJ)

Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, South Korea.
Division of Rheumatology, Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea, Suwon, South Korea.

Seung-Ah Yoo (SA)

Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, South Korea. youcap78@hanmail.net.
Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea. youcap78@hanmail.net.

Wan-Uk Kim (WU)

Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, South Korea. wan725@catholic.ac.kr.
Department of Internal Medicine, The Catholic University of Korea, Seoul, South Korea. wan725@catholic.ac.kr.

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