The novel RUNX3/p33 isoform is induced upon monocyte-derived dendritic cell maturation and downregulates IL-8 expression
| العنوان: | The novel RUNX3/p33 isoform is induced upon monocyte-derived dendritic cell maturation and downregulates IL-8 expression |
|---|---|
| المؤلفون: | Rocio T. Martinez-Nunez, Miguel A. Vega, María J. Alonso Martín, Ángeles Domínguez-Soto, Ángel Zaballos, María Teresa Corcuera, Amaya Puig-Kröger, María L. Toribio, Ana Dopazo, Noemí Aguilera-Montilla, Enrique Martin-Gayo, Fátima Sánchez-Cabo, Angel L. Corbí, Yoshiaki Ito, Yoram Groner |
| المساهمون: | Ministerio de Educación y Ciencia (España), Ministerio de Sanidad y Consumo (España), Instituto de Salud Carlos III, Fundación para la Investigación y la Prevención del Sida en España, Fundación Mutua Madrileña |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Myeloid, RUNX3, Immunology, CD11c, Down-Regulation, Biology, Monocytes, Chlorocebus aethiops, medicine, Immunology and Allergy, Animals, Humans, Protein Isoforms, RNA, Small Interfering, Transcription factor, Innate immunity, Tumor microenvironment, Innate immune system, U937 cell, IL-8, Chemotaxis, HEK 293 cells, Interleukin-8, Cell Differentiation, Hematology, Dendritic cell, Dendritic Cells, U937 Cells, digestive system diseases, Cell biology, medicine.anatomical_structure, Core Binding Factor Alpha 3 Subunit, HEK293 Cells, COS Cells, Mutagenesis, Site-Directed, Transcription |
| الوصف: | RUNX proteins are heterodimeric factors that play crucial roles during development and differentiation of cells of the immune system. The RUNX3 transcription factor controls lineage decisions during thymopoiesis and T-cell differentiation, and modulates myeloid cell effector functions. We now report the characterization of the human RUNX3/p33 isoform, generated by splicing out a Runt DNA-binding domain-encoding exon, and whose transcriptional activities differ from those of the prototypic RUNX3/p44 molecule. Unlike RUNX3/p44, RUNX3/p33 is induced upon maturation of monocyte-derived dendritic cells (MDDC), and is unable to transactivate the regulatory regions of the CD11a, CD11c and CD49e integrin genes. Overexpression of RUNX3/p33 in myeloid cell lines led to diminished expression of genes involved in inflammatory responses. Moreover, overexpression of RUNX3/p33 down-modulated the basal level of IL-8 production from immature monocyte-derived dendritic cells (MDDC). Besides, siRNA-mediated knock-down of RUNX3 led to diminished levels of IL-8 RNA in immature MDDC, and modulated the neutrophil-recruiting capacity of myeloid cell line supernatants. Since IL-8 promotes neutrophil chemotaxis and degranulation during inflammatory responses, and exerts mitogenic and angiogenic actions within tumor microenvironment, our results imply that myeloid RUNX3 expression regulates the recruitment of leukocytes towards inflammatory foci and might also contribute to human cancer progression. This work was supported by the Ministerio de Educación y Ciencia (grant BFU BFU2008-0149-BMC), Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (Spanish Network for the Research in Infectius Diseases, REIPI RD06/0008; and AIDS Research Network, RIS RD06/0006), Fundación para la Investigación y Prevención del SIDA en España (FIPSE 36422/03) and Fundación de Investigación Médica Mutua Madrileña (20060789) to ALC. APK is supported by Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (CP06/00199) |
| تدمد: | 1878-3279 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee848bdc6d5c3503e115f8839bd32d1cTest https://pubmed.ncbi.nlm.nih.gov/20615577Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ee848bdc6d5c3503e115f8839bd32d1c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18783279 |
|---|