ArticleJournal of immunology (Baltimore, Md. : 1950)2016
Dual Inhibition of Rip2 and IRAK1/4 Regulates IL-1β and IL-6 in Sarcoidosis Alveolar Macrophages and Peripheral Blood Mononuclear Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Novel Sarcoidosis Epitope Augments MHCII, CD80, and CD86 Expression and Promotes B-Cell Differentiation and IgG Production.American journal of respiratory cell and molecular biology · 2025Article
- Discovery of Two Novel Immunoepitopes and Development of a Peptide-based Sarcoidosis Immunoassay.American journal of respiratory and critical care medicine · 2024Article
- Article
- Adaptor molecules mediate negative regulation of macrophage inflammatory pathways: a closer look.Frontiers in immunology · 2024Review
- Recent advances in the development of RIPK2 modulators for the treatment of inflammatory diseases.Frontiers in pharmacology · 2023Review
- Modulatory role of macrophage migration inhibitory factor on cytokines and clinical features of sarcoidosis.Scientific reports · 2022Article
- Immune Modulation of Allergic Asthma by Early Pharmacological Inhibition of RIP2.ImmunoHorizons · 2020Article
- MKP-1 Modulates Mitochondrial Transcription Factors, Oxidative Phosphorylation, and Glycolysis.ImmunoHorizons · 2020Article
- Treatment of Sarcoidosis: A Multidisciplinary Approach.Frontiers in immunology · 2020Review
- Derangement of Metabolic and Lysosomal Gene Profiles in Response to Dexamethasone Treatment in Sarcoidosis.Frontiers in immunology · 2020Article
- Trained Innate Immunity Not Always Amicable.International journal of molecular sciences · 2019Review
- Interleukin-1 Receptor Associated Kinase 1 Mediates the Maintenance of Neuropathic Pain after Chronic Constriction Injury in Rats.Neurochemical research · 2019Article
- HIF-1α regulates IL-1β and IL-17 in sarcoidosis.eLife · 2019Article
- Tofacitinib Treatment and Molecular Analysis of Cutaneous Sarcoidosis.The New England journal of medicine · 2018Article
- Upregulated IRAK1 and IRAK4 promoting the production of IFN-γ and IL-17 in Behcet's disease.International ophthalmology · 2018Article
- Novel T7 Phage Display Library Detects Classifiers for Active Mycobacterium Tuberculosis Infection.Viruses · 2018Article
- Whole exome sequencing in three families segregating a pediatric case of sarcoidosis.BMC medical genomics · 2018Article
- Activation of Porcine Alveolar Macrophages by Actinobacillus pleuropneumoniae Lipopolysaccharide via the Toll-Like Receptor 4/NF-κB-Mediated Pathway.Infection and immunity · 2018Article
- K63-Linked Polyubiquitination on TRAF6 Regulates LPS-Mediated MAPK Activation, Cytokine Production, and Bacterial Clearance in Toll-Like Receptor 7/8 Primed Murine Macrophages.Frontiers in immunology · 2018Article
- RNA-sequencing Identifies Novel Pathways in Sarcoidosis Monocytes.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Sarcoidosis is a multisystem granulomatous disease of unknown etiology that primarily affects the lungs. Our previous work indicates that activation of p38 plays a pivotal role in sarcoidosis inflammatory response. Therefore, we investigated the upstream kinase responsible for activation of p38 in sarcoidosis alveolar macrophages (AMs) and PBMCs. We identified that sustained p38 phosphorylation in sarcoidosis AMs and PBMCs is associated with active MAPK kinase 4 but not with MAPK kinase 3/6. Additionally, we found that sarcoidosis AMs exhibit a higher expression of IRAK1, IRAK-M, and receptor interacting protein 2 (Rip2). Surprisingly, ex vivo treatment of sarcoidosis AMs or PBMCs with IRAK1/4 inhibitor led to a significant increase in IL-1β mRNA expression both spontaneously and in response to TLR2 ligand. However, a combination of Rip2 and IRAK-1/4 inhibitors significantly decreased both IL-1β and IL-6 production in sarcoidosis PBMCs and moderately in AMs. Importantly, a combination of Rip2 and IRAK-1/4 inhibitors led to decreased IFN-γ and IL-6 and decreased percentage of activated CD4(+)CD25(+) cells in PBMCs. These data suggest that in sarcoidosis, both pathways, namely IRAK and Rip2, are deregulated. Targeted modulation of Rip2 and IRAK pathways may prove to be a novel treatment for sarcoidosis.
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Registered trials
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