ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Inhibition of JAKs in macrophages increases lipopolysaccharide-induced cytokine production by blocking IL-10-mediated feedback.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
78 citing papers in PubMed, 127 citations in OpenAlex.
- The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis.Annals of the rheumatic diseases · 2015Trial
- Article
- Case Report: Clinical manifestations reported in a canine after ingesting ruxolitinib phosphate (OpzeluraFrontiers in veterinary science · 2026Article
- Paradoxical Activation of Entheseal Myeloid Cells by JAK1 and Tyk2 Inhibitors via Interleukin-10 Antagonism.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Tofacitinib ameliorates Campylobacter-induced intestinal pathology by suppressing IFNγ producing ILCs and T cells.Mucosal immunology · 2025Article
- The mechanisms behind heatstroke-induced intestinal damage.Cell death discovery · 2024Review
- Butyrate increases methylglyoxal production through regulation of the JAK2/Stat3/Nrf2/Glo1 pathway in castration‑resistant prostate cancer cells.Oncology reports · 2024Article
- Short-chain fatty acid-producing bacterial strains attenuate experimental ulcerative colitis by promoting M2 macrophage polarization via JAK/STAT3/FOXO3 axis inactivation.Journal of translational medicine · 2024Article
- Topical Delivery of Tofacitinib in Dermatology: The Promise of a Novel Therapeutic Class Using Biodegradable Dendritic Polyglycerol Sulfates.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Highly Active Myeloid Therapy for Cancer.ACS nano · 2023Article
- The Cytomegalovirus M35 Protein Directly Binds to the Interferon-β Enhancer and Modulates Transcription ofJournal of virology · 2023Article
- Selective Inhibitors of Janus Kinase 3 Modify Responses to Lipopolysaccharides by Increasing the Interleukin-10-to-Tumor Necrosis Factor α Ratio.ACS pharmacology & translational science · 2023Article
- Paradoxical activation of chronic lymphocytic leukemia cells by ruxolitinibFrontiers in oncology · 2023Article
- Pharmacokinetic Optimization of Small Molecule Janus Kinase 3 Inhibitors to Target Immune Cells.ACS pharmacology & translational science · 2022Article
- Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity.Cell reports · 2022Article
- Protective Effect of CP690550 in MPTP-Induced Parkinson's Like Behavioural, Biochemical and Histological Alterations in Mice.Neurotoxicity research · 2022Article
- Immunomodulating Activity ofJournal of fungi (Basel, Switzerland) · 2022Article
- Repolarization of Unbalanced Macrophages: Unmet Medical Need in Chronic Inflammation and Cancer.International journal of molecular sciences · 2022Review
- Ruxolitinib inhibits cytokine production by human lung macrophages without impairing phagocytic ability.Frontiers in pharmacology · 2022Article
- Macrophages and glial cells: Innate immune drivers of inflammatory arthritic pain perception from peripheral joints to the central nervous system.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
18 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
Macrophages are an important source of cytokines following infection. Stimulation of macrophages with TLR agonists results in the secretion of TNF-α, IL-6, and IL-12, and the production of these cytokines is controlled by multiple feedback pathways. Macrophages also produce IL-10, which acts to inhibit proinflammatory cytokine production by macrophages via a JAK/STAT3-dependent pathway. We show in this paper that, Ruxolitinib, a recently described selective inhibitor of JAKs, increases TNF, IL-6, and IL-12 secretion in mouse bone marrow-derived macrophages stimulated with LPS. This effect is largely due to its ability to block IL-10-mediated feedback inhibition on cytokine transcription in macrophages. Similar results were also obtained with a second structurally unrelated Jak inhibitor, Tofacitinib. In addition, LPS induced the production of IFN-β, which was then able to activate JAKs in macrophages, resulting in the stimulation of STAT1 phosphorylation. The initial induction of IL-10 was independent of JAK signaling; however, inhibition of JAKs did reduce IL-10 secretion at later time points. This reflected a requirement for the IFN-β feedback loop to sustain IL-10 transcription following LPS stimulation. In addition to IL-10, IFN-β also helped sustain IL-6 and IL-12 transcription. Overall, these results suggest that inhibition of JAKs may increase the inflammatory potential of macrophages stimulated with TLR4 agonists.
Indexed as
Identifiers
What OpenQuestion holds
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.