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Controlled macrophage differentiation and activation in the initiation and resolution of inflammation is crucial for averting progression to chronic inflammatory and autoimmune diseases. Here we show a negative feedback mechanism for proinflammatory IFN-γ activation of macrophages driven by macrophage-associated matrix metalloproteinase 12 (MMP12). Through C-terminal truncation of IFN-γ at 135Glu↓Leu136 the IFN-γ receptor-binding site was efficiently removed thereby reducing JAK-STAT1 signaling and IFN-γ activation of proinflammatory macrophages. In acute peritonitis this signature was absent in Mmp12 -/- mice and recapitulated in Mmp12 +/+ mice treated with a MMP12-specific inhibitor. Similarly, loss-of-MMP12 increases IFN-γ-dependent proinflammatory markers and iNOS+/MHC class II+ macrophage accumulation with worse lymphadenopathy, arthritic synovitis and lupus glomerulonephritis. In active human systemic lupus erythematosus, MMP12 levels were lower and IFN-γ higher compared to treated patients or healthy individuals. Hence, macrophage proteolytic truncation of IFN-γ attenuates classical activation of macrophages as a prelude for resolving inflammation.
Pubmed ID: 29925830
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Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsCollection of data of protein sequence and functional information. Resource for protein sequence and annotation data. Consortium for preservation of the UniProt databases: UniProt Knowledgebase (UniProtKB), UniProt Reference Clusters (UniRef), and UniProt Archive (UniParc), UniProt Proteomes. Collaboration between European Bioinformatics Institute (EMBL-EBI), SIB Swiss Institute of Bioinformatics and Protein Information Resource. Swiss-Prot is a curated subset of UniProtKB.
View all literature mentionsAn independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsA division of Applied Biosystems selling products for the isolation, detection, quantification, amplification, and characterization of RNA.
View all literature mentionsCommercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.
View all literature mentionsSoftware tool as convolutional neural network to quantify natural selection from genomic data.Supervised machine learning algorithm to predict natural selection and estimate selection coefficients from population genomic data. Can be used to estimate any parameter of interest from evolutionary population genetics model.
View all literature mentionsInternational functional genomics data collection generated from microarray or next-generation sequencing (NGS) platforms. Repository of functional genomics data supporting publications. Provides genes expression data for reuse to the research community where they can be queried and downloaded. Integrated with the Gene Expression Atlas and the sequence databases at the European Bioinformatics Institute. Contains a subset of curated and re-annotated Archive data which can be queried for individual gene expression under different biological conditions across experiments. Data collected to MIAME and MINSEQE standards. Data are submitted by users or are imported directly from the NCBI Gene Expression Omnibus.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsResource for reuse, sharing and meta-analysis of expression profiling data. Database and set of tools for meta analysis, reuse and sharing of genomics data. Targeted at analysis of gene expression profiles. Users can search, access and visualize coexpression and differential expression results.
View all literature mentionsAlgorithm for MATLAB and the EEGLAB toolbox that enables the automatic detection of independent components from an ICA that represent event-related brain potentials. It performs automatic Independent Component (IC) selection with respect to the contributions of the ICs to a certain ERP.
View all literature mentionsThe TIGR database is a collection of plant transcript sequences. Transcript assemblies are searchable using BLAST and accession number. The construction of plant transcript assemblies (TAs) is similar to the TIGR gene indices. The sequences that are used to build the plant TAs are expressed transcripts collected from dbEST (ESTs) and the NCBI GenBank nucleotide database (full length and partial cDNAs). "Virtual" transcript sequences derived from whole genome annotation projects are not included. All plant species for which more than 1,000 ESTs or cDNA sequences are available are included in this project. TAs are clustered and assembled using the TGICL tool (Pertea et al., 2003), Megablast (Zhang et al., 2000) and the CAP3 assembler (Huang and Madan, 1999). TGICL is a wrapper script which invokes Megablast and CAP3. Sequences are initially clustered based on an all-against-all comparisons using Megablast. The initial clusters are assembled to generate consensus sequences using CAP3. Assembly criteria include a 50 bp minimum match, 95% minimum identity in the overlap region and 20 bp maximum unmatched overhangs. Any EST/cDNA sequences that are not assembled into TAs are included as singletons. All singletons retain their GenBank accession numbers as identifiers. Plant TA identifiers are of the form TAnumber_taxonID, where number is a unique numerical identifier of the transcript assembly and taxonID represents the NCBI taxon id. In order to provide annotation for the TAs, each TA/singleton was aligned to the UniProt Uniref database. For release 1 TAs, a masked version of the Uniref90 database was used. For release 2 and onwards, a masked version of the UniRef100 database is used. Alignments were required to have at least 20% identity and 20% coverage. The annotation for the protein with the best alignment to each TA or singleton was used as the annotation for that sequence. Additionally, the relative orientation of each TA/singleton to the best matching protein sequence was used to determine the orientation of each TA/singleton. Some sequences did not have alignments to the protein database that met our quality criteria, and those sequences have neither annotation nor orientation assignments. The release number for the plant TAs refers to the release version for a particular species. For the initial build, all TA sets are of version 1. Subsequent TA updates for new releases will be carried out when the percentage increase of the EST and cDNA counts exceeds 10% of the previous release and when the increase contains more than 1,000 new sequences. New releases will also include additional plant species with more than 1,000 EST or cDNA sequences that have become publicly available.
View all literature mentionsCell line THP-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line RAW 264.7 is a Cancer cell line with a species of origin Mus musculus
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