ArticleArthritis research & therapy2006
The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis.
Article in Arthritis research & therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
164 citing papers in PubMed, 1 synthesis or guideline pooled it, 318 citations in OpenAlex.
- Neutrophil-Enriched Biomarkers and Long-Term Prognosis in Acute Coronary Syndrome: a Systematic Review and Meta-analysis.Journal of cardiovascular translational research · 2024Pooled it
- Circulating S100A8 and S100A9 protein levels in plasma of patients with acquired aplastic anemia and myelodysplastic syndromes.Cytokine · 2019Trial
- Increased expression of damage-associated molecular patterns (DAMPs) in osteoarthritis of human knee joint compared to hip joint.Molecular and cellular biochemistry · 2017Trial
- Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.Arthritis & rheumatology (Hoboken, N.J.) · 2017Trial
- S100A9 Induces RANKL Expression in Osteocytes Utilizing IL-6/sIL-6R Combination and gp130 Signaling Pathways.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The Role of S100A8/A9 in Autoimmune Eye Diseases: From Pathogenesis to Targeted Therapy.Investigative ophthalmology & visual science · 2026Review
- S100A8/A9 and S100A12 Proteins and Macrophage Polarization: Therapeutic Targets in Atherosclerosis.Biomolecules · 2026Review
- Polygonatum sibiricum polysaccharides regulate chondrocyte inflammation and metabolism via S100A9 inhibition-mediated autophagy promotion to ameliorate osteoarthritis.BMC complementary medicine and therapies · 2026Article
- Programmed cell death-related gene S100A9 promotes macrophage M1 polarization and chondrocyte apoptosis in rheumatoid arthritis.Biology direct · 2026Article
- Identification of rheumatoid arthritis manganese metabolism-related diagnostic biomarkers through bulk and single-cell RNA sequencing analysis.Clinical rheumatology · 2026Article
- Calprotectin and serum amyloid A for disease activity assessment in giant cell arteritis and polymyalgia rheumatica: results from a prospective single-centre cohort study.Rheumatology international · 2026Article
- Innate-immune crosstalk orchestrates T cell-mediated rejection in kidney transplants.Frontiers in immunology · 2026Article
- Adipocyte death promotes hepatic infiltration of S100A8+ macrophages and steatotic liver disease progression in mice.The Journal of clinical investigation · 2025Article
- Deep phenotyping of a modified diabetic cardiomyopathy mouse model which reflects clinical disease progression.Diabetology & metabolic syndrome · 2025Article
- Construction of a glycolysis-related diagnostic model for osteoarthritis through integrated bioinformatics analysis and machine learning.Journal of orthopaedic surgery and research · 2025Article
- Intestinal epithelium-derived IL-34 reprograms macrophages to mitigate gastrointestinal tract graft-versus-host disease.Science translational medicine · 2025Article
- Characteristics and multi-omics analysis of spontaneous spondyloarthritis in non-human primates: Case report.Heliyon · 2025Article
- Serum calprotectin correlates stronger with inflammation and disease activity in ACPA positive than ACPA negative rheumatoid arthritis.Rheumatology (Oxford, England) · 2025Article
- S100 proteins as a key immunoregulatory mechanism for NLRP3 inflammasome.Frontiers in immunology · 2025Review
- S100A8/A9 drives monocytes towards M2-like macrophage differentiation and associates with M2-like macrophages in osteoarthritic synovium.Rheumatology (Oxford, England) · 2025Article
104 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
S100A8 and S100A9, two Ca2+-binding proteins of the S100 family, are secreted as a heterodimeric complex (S100A8/A9) from neutrophils and monocytes/macrophages. Serum and synovial fluid levels of S100A8, S100A9, and S100A8/A9 were all higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA), with the S100A8/A9 heterodimer being prevalent. By two-color immunofluorescence labeling, S100A8/A9 antigens were found to be expressed mainly by infiltrating CD68+ macrophages in RA synovial tissue (ST). Isolated ST cells from patients with RA spontaneously released larger amounts of S100A8/A9 protein than did the cells from patients with OA. S100A8/A9 complexes, as well as S100A9 homodimers, stimulated the production of proinflammatory cytokines, such as tumor necrosis factor alpha, by purified monocytes and in vitro-differentiated macrophages. S100A8/A9-mediated cytokine production was suppressed significantly by p38 mitogen-activated protein kinase (MAPK) inhibitors and almost completely by nuclear factor kappa B (NF-kappaB) inhibitors. NF-kappaB activation was induced in S100A8/A9-stimulated monocytes, but this activity was not inhibited by p38 MAPK inhibitors. These results indicate that the S100A8/A9 heterodimer, secreted extracellularly from activated tissue macrophages, may amplify proinflammatory cytokine responses through activation of NF-kappaB and p38 MAPK pathways in RA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.