ArticleImmunology2003
Differential regulation of interleukin-12 p40 and p35 induction via Erk mitogen-activated protein kinase-dependent and -independent mechanisms and the implications for bioactive IL-12 and IL-23 responses.
Article in Immunology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 117 citations in OpenAlex.
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- An optimized cocktail of small molecule inhibitors promotes the maturation of dendritic cells in GM-CSF mouse bone marrow culture.Frontiers in immunology · 2023Article
- A novel lipidic peptide with potential to promote balanced effector-regulatory T cell responses.Scientific reports · 2022Article
- Macrophage-mediated RON signaling supports breast cancer growth and progression through modulation of IL-35.Oncogene · 2022Article
- The Effects of Simulated Microgravity on Macrophage Phenotype.Biomedicines · 2021Article
- Iron Released after Cryo-Thermal Therapy Induced M1 Macrophage Polarization, Promoting the Differentiation of CD4International journal of molecular sciences · 2021Article
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- Infective Larvae ofFrontiers in immunology · 2018Article
- The Eukaryotic Elongation Factor 1 Alpha (eEF1α) from the Parasite Leishmania infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine (PC).Molecules (Basel, Switzerland) · 2017Article
- Dendritic cells provide a therapeutic target for synthetic small molecule analogues of the parasitic worm product, ES-62.Scientific reports · 2017Article
- Inhibition of 6-phosphofructo-2-kinase suppresses fibroblast-like synoviocytes-mediated synovial inflammation and joint destruction in rheumatoid arthritis.British journal of pharmacology · 2017Article
- Dendritic cells and parasites: from recognition and activation to immune response instruction.Seminars in immunopathology · 2017Review
- Differential immunomodulation in human monocytes versus macrophages by filarial cystatin.PloS one · 2017Article
- New Data on Human Macrophages Polarization byFrontiers in immunology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Bioactive interleukin (IL)-12 is a 70 000-molecular weight (MW) heterodimeric cytokine comprising p40 and p35 chains. However, p40 can also form homodimers that antagonize bioactive IL-12 or heterodimerize with p19 to form IL-23, which exhibits overlapping yet distinct functions to that of IL-12. We now define distinct signalling mechanisms that regulate lipopolysaccharide (LPS)-mediated induction of IL-12 p40 and p35 in macrophages and which may therefore provide therapeutic targets for precise and specific fine-tuning of cytokine responses. Thus, whilst LPS-induced p38 mitogen-activated protein kinase (MAPkinase) activation is required for the induction of both p40 and p35 subunits, Erk MAPkinase signalling mediates negative feedback regulation of p40, but not p35, production. Such Erk MAPkinase activation is downstream of calcium influx and targets LPS-induced IL-12 p40 transcription by suppressing the synthesis of the transcription factor, interferon regulatory factor-1 (IRF-1). In contrast, negative regulation of the p35 subunit of IL-12 occurs via a calcium-dependent, but Erk-independent, mechanism, which is likely to involve nuclear factor (NF)-kappa B signalling. Finally, the importance of both Erk and p38 MAPkinases in differentially regulating IL-12 p40 and p35 production is underscored by each being targeted by ES-62, a product secreted by parasitic filarial nematodes to polarize the immune system towards an anti-inflammatory phenotype conducive to their survival.
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