ArticleArthritis research & therapy2016
Lymphatic endothelial cells efferent to inflamed joints produce iNOS and inhibit lymphatic vessel contraction and drainage in TNF-induced arthritis in mice.
Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Vascular-lymphatic dual circulation in bone health and disease: Mechanistic coupling and translational therapeutics.Journal of orthopaedic translation · 2026Review
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- Complement Anaphylatoxin C5a-Induced Mouse Lymphatic Functions Modulate Interactions Between Endothelial Cells and T Lymphocytes.Immune network · 2026Article
- The spinal lymphatic system: an emerging pathway bridging fluid homeostasis, immunity, and disease.Bone research · 2026Review
- Vanadyl Acetylacetonate and Berberine Synergistically Ameliorate Diabetes-induced Vascular Dysfunction and Reduce Endothelial Toxicity through ERK and Akt Regulation.Biological trace element research · 2026Article
- Lymphatic-immune interactions in the musculoskeletal system.Frontiers in immunology · 2025Review
- Anti-inflammatory and anti-arthritic activities of ethanolic extract of Myxopyrum serratulum A.W. Hill.Laboratory animal research · 2024Article
- Lymphatic vessels: roles and potential therapeutic intervention in rheumatoid arthritis and osteoarthritis.Theranostics · 2024Review
- The Enigmas of Lymphatic Muscle Cells: Where Do They Come From, How Are They Maintained, and Can They Regenerate?Current rheumatology reviews · 2023Review
- Engineering approaches to investigate the roles of lymphatics vessels in rheumatoid arthritis.Microcirculation (New York, N.Y. : 1994) · 2023Review
- Current understanding of osteoarthritis pathogenesis and relevant new approaches.Bone research · 2022Review
- Persistent popliteal lymphatic muscle cell coverage defects despite amelioration of arthritis and recovery of popliteal lymphatic vessel function in TNF-Tg mice following anti-TNF therapy.Scientific reports · 2022Article
- Single-cell transcriptomics of popliteal lymphatic vessels and peripheral veins reveals altered lymphatic muscle and immune cell populations in the TNF-Tg arthritis model.Arthritis research & therapy · 2022Article
- Lymphatic muscle cells contribute to dysfunction of the synovial lymphatic system in inflammatory arthritis in mice.Arthritis research & therapy · 2021Article
- Article
- Regulation of lymphatic function and injury by nitrosative stress in obese mice.Molecular metabolism · 2020Article
- Ginsenoside Rg1 promotes lymphatic drainage and improves chronic inflammatory arthritis.Journal of musculoskeletal & neuronal interactions · 2020Article
- Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging.Fluids and barriers of the CNS · 2020Article
- Lymph Node Stromal Cells: Mapmakers of T Cell Immunity.International journal of molecular sciences · 2020Review
- Altered Lymphatic Vessel Anatomy and Markedly Diminished Lymph Clearance in Affected Hands of Patients With Active Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundIn this study, we sought to determine the cellular source of inducible nitric oxide synthase (iNOS) induced in lymphatic endothelial cells (LECs) in response to tumor necrosis factor (TNF), the effects of iNOS on lymphatic smooth muscle cell (LSMC) function and on the development of arthritis in TNF-transgenic (TNF-Tg) mice, and whether iNOS inhibitors improve lymphatic function and reduce joint destruction in inflammatory erosive arthritis.
methodsWe used quantitative polymerase chain reactions, immunohistochemistry, histology, and near-infrared imaging to examine (1) iNOS expression in podoplanin + LECs and lymphatic vessels from wild-type (WT) and TNF-Tg mice, (2) iNOS induction by TNF in WT LECs, (3) the effects of iNOS inhibitors on expression of functional muscle genes in LSMCs, and (4) the effects of iNOS inhibitors on lymphatic vessel contraction and drainage, as well as the severity of arthritis, in TNF-Tg mice.
resultsLECs from TNF-Tg mice had eight fold higher iNOS messenger RNA levels than WT cells, and iNOS expression was confirmed immunohistochemically in podoplanin + LECs in lymphatic vessels from inflamed joints. TNF (0.1 ng/ml) increased iNOS levels 40-fold in LECs. LSMCs cocultured with LECs pretreated with TNF had reduced expression of functional muscle genes. This reduction was prevented by ferulic acid, which blocked nitric oxide production. Local injection of L-N(6)-(1-iminoethyl)lysine 5-tetrazole-amide into inflamed paws of TNF-Tg mice resulted in recovery of lymphatic vessel contractions and drainage. Treatment of TNF-Tg mice with ferulic acid reduced synovial inflammation as well as cartilage and bone erosion, and it also restored lymphatic contraction and drainage.
conclusionsiNOS is produced primarily by LECs in lymphatic vessel efferent from inflamed joints of TNF-Tg mice in response to TNF and inhibits LSMC contraction and lymph drainage. Ferulic acid represents a potential new therapy to restore lymphatic function and thus improve inflammatory arthritis by inhibiting local production of nitric oxide by LSMCs.
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