Ac2PIM-responsive miR-150 and miR-143 target receptor-interacting protein kinase 2 and transforming growth factor beta-activated kinase 1 to suppress NOD2-induced immunomodulators
| Autor: | Sahana Holla, Kithiganahalli Narayanaswamy Balaji, Vibha Udupa, Martine Gilleron, Praveen Prakhar, Devram Sampat Ghorpade, Germain Puzo |
|---|---|
| Přispěvatelé: | Indian Institute of Science [Bangalore] (IISc Bangalore), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_treatment
Nod2 Signaling Adaptor Protein Suppressor of Cytokine Signaling Proteins [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Nitric Oxide Biochemistry Cell Line Epigenesis Genetic chemistry.chemical_compound Mice Phosphatidylinositol 3-Kinases Receptor-Interacting Protein Serine-Threonine Kinase 2 NOD2 medicine Animals Immunologic Factors Molecular Biology ComputingMilieux_MISCELLANEOUS Microbiology & Cell Biology Mice Knockout Innate immune system MAP kinase kinase kinase Macrophages Polysaccharides Bacterial Cell Biology Transforming growth factor beta MAP Kinase Kinase Kinases Immunity Innate Toll-Like Receptor 2 Cell biology Mice Inbred C57BL TLR2 MicroRNAs Cytokine chemistry Matrix Metalloproteinase 9 Cyclooxygenase 2 Suppressor of Cytokine Signaling 3 Protein Receptor-Interacting Protein Serine-Threonine Kinases biology.protein Additions and Corrections Signal transduction Mitogen-Activated Protein Kinases Acetylmuramyl-Alanyl-Isoglutamine Muramyl dipeptide Protein Binding Signal Transduction |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2015, 290 (44), pp.26576-26586. ⟨10.1074/jbc.M115.662817⟩ |
| ISSN: | 1083-351X 0021-9258 |
| DOI: | 10.1074/jbc.M115.662817⟩ |
| Popis: | Specific and coordinated regulation of innate immune receptor-driven signaling networks often determines the net outcome of the immune responses. Here, we investigated the cross-regulation of toll-like receptor (TLR)2 and nucleotide-binding oligomerization domain (NOD)2 pathways mediated by Ac2PIM, a tetra-acylated form of mycobacterial cell wall component and muramyl dipeptide (MDP), a peptidoglycan derivative respectively. While Ac2PIM treatment of macrophages compromised their ability to induce NOD2-dependent immunomodulators like cyclooxygenase (COX)-2, suppressor of cytokine signaling (SOCS)-3, and matrix metalloproteinase (MMP)-9, no change in the NOD2-responsive NO, TNF-alpha, VEGF-A, and IL-12 levels was observed. Further, genome-wide microRNA expression profiling identified Ac2PIM-responsive miR-150 and miR-143 to target NOD2 signaling adaptors, RIP2 and TAK1, respectively. Interestingly, Ac2PIM was found to activate the SRC-FAK-PYK2-CREB cascade via TLR2 to recruit CBP/P300 at the promoters of miR-150 and miR-143 and epigenetically induce their expression. Loss-of-function studies utilizing specific miRNA inhibitors establish that Ac2PIM, via the miRNAs, abrogate NOD2-induced PI3K-PKC delta-MAPK pathway to suppress beta-catenin-mediated expression of COX-2, SOCS-3, and MMP-9. Our investigation has thus underscored the negative regulatory role of Ac2PIM-TLR2 signaling on NOD2 pathway which could broaden our understanding on vaccine potential or adjuvant utilities of Ac2PIM and/or MDP. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|