ArticleImmunology2009
Induction of lymphotoxin-alpha by interleukin-12 p40 homodimer, the so-called biologically inactive molecule, but not IL-12 p70.
Article in Immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Association of Interleukin 23 Receptor Polymorphisms with Predisposition to Rheumatoid Arthritis: An Updated Meta and Trial Sequential Analysis.Biochemical genetics · 2024Pooled it
- Trial
- Corrected Version: IL-12 p40 Monomer is Different from Other IL-12 Family Members to Selectively Inhibit IL-12Rβ1 Internalization and Suppress EAE.Journal of clinical & experimental immunology · 2026Article
- LT-α Facilitates the Aerobic Glycolysis and M1 Polarization of Macrophages by Activating the NF-κB Signaling Pathway in Intervertebral Disc Degeneration.Journal of inflammation research · 2025Article
- Hidradenitis Suppurativa: An Understanding of Genetic Factors and Treatment.Biomedicines · 2024Review
- Article
- Interleukin-23 Involved in Fibrotic Autoimmune Diseases: New Discoveries.Journal of clinical medicine · 2023Review
- Article
- The regulatory mechanism and potential application of IL-23 in autoimmune diseases.Frontiers in pharmacology · 2022Review
- Role of the IL-23/IL-17 Pathway in Rheumatic Diseases: An Overview.Frontiers in immunology · 2021Review
- IL-12 and IL-23-Close Relatives with Structural Homologies but Distinct Immunological Functions.Cells · 2020Review
- IL-12 p40 monomer is different from other IL-12 family members to selectively inhibit IL-12Rβ1 internalization and suppress EAE.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Calpain mediated expansion of CD4+ cytotoxic T cells in rodent models of Parkinson's disease.Experimental neurology · 2020Article
- Peripheral-Central Neuroimmune Crosstalk in Parkinson's Disease: What Do Patients and Animal Models Tell Us?Frontiers in neurology · 2019Review
- Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome.Journal of neuroinflammation · 2017Article
- Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12-IFN-γ.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Regulation of IL-12p40 by HIF controls Th1/Th17 responses to prevent mucosal inflammation.Mucosal immunology · 2017Article
- Lignin-graft-Polyoxazoline Conjugated Triazole a Novel Anti-Infective Ointment to Control Persistent Inflammation.Scientific reports · 2017Article
- Interleukin-12 (IL-12), but not IL-23, induces the expression of IL-7 in microglia and macrophages: implications for multiple sclerosis.Immunology · 2014Article
- Role of the Lymphotoxin/LIGHT System in the Development and Maintenance of Reticular Networks and Vasculature in Lymphoid Tissues.Frontiers in immunology · 2014Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Interleukin-12 (IL-12) p70 (p40:p35) is a bioactive cytokine and its biological functions are becoming clear. On the other hand, the IL-12 p40 homodimer (p40(2)) was considered an inactive or inhibitory molecule and its functions are poorly understood. It has been reported that increased expression of lymphotoxin-alpha (Lt-alpha) in the central nervous system as well as in peripheral immune cells is associated with multiple sclerosis and experimental allergic encephalomyelitis. Here we describe that p40(2) induces the expression of Lt-alpha in primary mouse and human microglia, BV-2 microglial cells, splenic macrophages, RAW 264.7 cells and splenic T cells. Interestingly, IL-12 p70 was either unable to induce Lt-alpha or was a very weak inducer of Lt-alpha in these cell types. Consistently, p40(2), but not p70, induced Lt-alpha promoter-driven luciferase activity in microglial cells. Among various stimuli tested, p40(2) emerged as the most potent followed by IL-16, lipopolyaccharide and double-stranded RNA in inducing the activation of Lt-alpha promoter in microglial cells. Furthermore, an increase in Lt-alpha messenger RNA expression by overexpression of p40, but not p35, complementary DNA and induction of Lt-alpha expression by p40(2) in microglia isolated from IL-12p35(-/-) mice confirm that p40, but not p35, is responsible for the induction of Lt-alpha. Finally, by using primary microglia from IUL-12 receptor beta1 deficient (IL-12Rbeta1(-/-)) and IL-12Rbeta2(-/-) mice, we demonstrate that p40(2) induced the expression of Lt-alpha in microglia and macrophages via IL-12Rbeta1, but not IL-12Rbeta2. These studies delineate a novel biological function of p40(2) that is absent in IL-12.
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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.