ArticleImmunological investigations2004
p38 MAPK regulates IL-1beta induced IL-6 expression through mRNA stability in osteoblasts.
Article in Immunological investigations, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
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- Microglia shield the murine brain from damage mediated by the cytokines IL-6 and IFN-α.Frontiers in immunology · 2022Article
- Histamine causes an imbalance between pro-angiogenic and anti-angiogenic factors in the retinal pigment epithelium of diabetic retina via H4 receptor/p38 MAPK axis.BMJ open diabetes research & care · 2020Article
- Functionalized nanoparticles containing MKP-1 agonists reduce periodontal bone loss.Journal of periodontology · 2019Article
- Galectin-3 is an amplifier of the interleukin-1β-mediated inflammatory response in corneal keratinocytes.Immunology · 2018Article
- The in vitro effects of macrophages on the osteogenic capabilities of MC3T3-E1 cells encapsulated in a biomimetic poly(ethylene glycol) hydrogel.Acta biomaterialia · 2018Article
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- Liver X Receptor Agonist TO901317 Attenuates Paraquat-Induced Acute Lung Injury through Inhibition of NF-BioMed research international · 2017Article
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- p38 MAPK Signaling in Osteoblast Differentiation.Frontiers in cell and developmental biology · 2016Review
- Piperine inhibits IL-1β-induced IL-6 expression by suppressing p38 MAPK and STAT3 activation in gastric cancer cells.Molecular and cellular biochemistry · 2015Article
- Stimulation of mesenchymal stromal cells (MSCs) via TLR3 reveals a novel mechanism of autocrine priming.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- CB2 receptor activation ameliorates the proinflammatory activity in acute lung injury induced by paraquat.BioMed research international · 2014Article
- Peripheral injection of SB203580 inhibits the inflammatory-dependent synthesis of proinflammatory cytokines in the hypothalamus.BioMed research international · 2014Article
- The TGFβ-induced phosphorylation and activation of p38 mitogen-activated protein kinase is mediated by MAP3K4 and MAP3K10 but not TAK1.Open biology · 2013Article
- Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Sustained mitogen-activated protein kinase activation with Aggregatibacter actinomycetemcomitans causes inflammatory bone loss.Molecular oral microbiology · 2012Article
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Authors and funding
5 authors at 1 institution in 3 countries.
Funding
Abstract
Osteoblast-derived IL-6 functions in coupled bone turnover by supporting osteoclastogenesis favoring bone resorption instead of bone deposition. Gene regulation of IL-6 is complex occurring both at transcription and post-transcription levels. The focus of this paper is at the level of mRNA stability, which is important in IL-6 gene regulation. Using the MC3T3-E1 as an osteoblastic model, IL-6 secretion was dose dependently decreased by SB203580, a p38 MAPK inhibitor. Steady state IL-6 mRNA was decreased with SB203580 (2 microM) ca. 85% when stimulated by IL-1beta (1-5 ng/ml). These effects require de novo protein synthesis as they were inhibited by cycloheximide. p38 MAPK had minor effects on proximal IL-6 promoter activity in reporter gene assays. A more significant effect on IL-6 mRNA stability was observed in the presence of SB203580. Western blot analysis confirmed that SB203580 inhibited p38 MAP kinase, in response to IL-1beta in a dose dependent manner in MC3T3-E1 cells. Stably transfected MC3T3-E1 reporter cell lines (MC6) containing green fluorescent protein (GFP) with the 3'untranslated region of IL-6 were constructed. Results indicated that IL-1beta, TNFalpha, LPS but not parathyroid hormone (PTH) could increase GFP expression of these reporter cell lines. Endogenous IL-6 and reporter gene eGFP-IL-6 3'UTR mRNA was regulated by p38 in MC6 cells. In addition, transient transfection of IL-6 3'UTR reporter cells with immediate upstream MAP kinase kinase-3 and -6 increased GFP expression compared to mock transfected controls. These results indicate that p38 MAPK regulates IL-1beta-stimulated IL-6 at a post transcriptional mechanism and one of the primary targets of IL-6 gene regulation is the 3'UTR of IL-6.
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