PubMed:19233845 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/19233845","sourcedb":"PubMed","sourceid":"19233845","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/19233845","text":"GLEPP1/protein-tyrosine phosphatase phi inhibitors block chemotaxis in vitro and in vivo and improve murine ulcerative colitis.\nWe describe novel, cell-permeable, and bioavailable salicylic acid derivatives that are potent and selective inhibitors of GLEPP1/protein-tyrosine phosphatase . Two previously described GLEPP1 substrates, paxillin and Syk, are both required for cytoskeletal rearrangement and cellular motility of leukocytes in chemotaxis. We show here that GLEPP1 inhibitors prevent dephosphorylation of Syk1 and paxillin in resting cells and block primary human monocyte and mouse bone marrow-derived macrophage chemotaxis in a gradient of monocyte chemotactic protein-1. In mice, the GLEPP1 inhibitors also reduce thioglycolate-induced peritoneal chemotaxis of neutrophils, lymphocytes, and macrophages. In murine disease models, the GLEPP1 inhibitors significantly reduce severity of contact hypersensitivity, a model for allergic dermatitis, and dextran sulfate sodium-induced ulcerative colitis, a model for inflammatory bowel disease. Taken together, our data provide confirmation that GLEPP1 plays an important role in controlling chemotaxis of multiple types of leukocytes and that pharmacological inhibition of this phosphatase may have therapeutic use.","tracks":[{"project":"sentences","denotations":[{"id":"T1","span":{"begin":0,"end":127},"obj":"Sentence"},{"id":"T2","span":{"begin":128,"end":288},"obj":"Sentence"},{"id":"T3","span":{"begin":289,"end":450},"obj":"Sentence"},{"id":"T4","span":{"begin":451,"end":684},"obj":"Sentence"},{"id":"T5","span":{"begin":685,"end":817},"obj":"Sentence"},{"id":"T6","span":{"begin":818,"end":1052},"obj":"Sentence"},{"id":"T7","span":{"begin":1053,"end":1274},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":127},"obj":"Sentence"},{"id":"T2","span":{"begin":128,"end":288},"obj":"Sentence"},{"id":"T3","span":{"begin":289,"end":450},"obj":"Sentence"},{"id":"T4","span":{"begin":451,"end":684},"obj":"Sentence"},{"id":"T5","span":{"begin":685,"end":817},"obj":"Sentence"},{"id":"T6","span":{"begin":818,"end":1052},"obj":"Sentence"},{"id":"T7","span":{"begin":1053,"end":1274},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"}]},{"project":"NCBITAXON","denotations":[{"id":"T1","span":{"begin":569,"end":574},"obj":"OrganismTaxon"},{"id":"T2","span":{"begin":588,"end":593},"obj":"OrganismTaxon"},{"id":"T4","span":{"begin":688,"end":692},"obj":"OrganismTaxon"}],"attributes":[{"id":"A1","pred":"db_id","subj":"T1","obj":"9606"},{"id":"A2","pred":"db_id","subj":"T2","obj":"10088"},{"id":"A3","pred":"db_id","subj":"T2","obj":"10090"},{"id":"A4","pred":"db_id","subj":"T4","obj":"10088"},{"subj":"T1","pred":"source","obj":"NCBITAXON"},{"subj":"T2","pred":"source","obj":"NCBITAXON"},{"subj":"T4","pred":"source","obj":"NCBITAXON"}]},{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":108,"end":126},"obj":"Disease"},{"id":"T3","span":{"begin":907,"end":923},"obj":"Disease"},{"id":"T5","span":{"begin":937,"end":956},"obj":"Disease"},{"id":"T6","span":{"begin":993,"end":1011},"obj":"Disease"},{"id":"T8","span":{"begin":1025,"end":1051},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005101"},{"id":"A2","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0009960"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0000605"},{"id":"A4","pred":"mondo_id","subj":"T3","obj":"http://purl.obolibrary.org/obo/MONDO_0005271"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/MONDO_0004980"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0005101"},{"id":"A7","pred":"mondo_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/MONDO_0009960"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/MONDO_0005265"},{"subj":"T1","pred":"source","obj":"mondo_disease"},{"subj":"T3","pred":"source","obj":"mondo_disease"},{"subj":"T5","pred":"source","obj":"mondo_disease"},{"subj":"T6","pred":"source","obj":"mondo_disease"},{"subj":"T8","pred":"source","obj":"mondo_disease"}]},{"project":"Glycosmos6-MAT","denotations":[{"id":"T1","span":{"begin":594,"end":605},"obj":"http://purl.obolibrary.org/obo/MAT_0000084"},{"id":"T2","span":{"begin":594,"end":598},"obj":"http://purl.obolibrary.org/obo/MAT_0000299"}],"attributes":[{"subj":"T1","pred":"source","obj":"Glycosmos6-MAT"},{"subj":"T2","pred":"source","obj":"Glycosmos6-MAT"}]},{"project":"Inflammaging","denotations":[{"id":"T1","span":{"begin":0,"end":127},"obj":"Sentence"},{"id":"T2","span":{"begin":128,"end":288},"obj":"Sentence"},{"id":"T3","span":{"begin":289,"end":450},"obj":"Sentence"},{"id":"T4","span":{"begin":451,"end":684},"obj":"Sentence"},{"id":"T5","span":{"begin":685,"end":817},"obj":"Sentence"},{"id":"T6","span":{"begin":818,"end":1052},"obj":"Sentence"},{"id":"T7","span":{"begin":1053,"end":1274},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":127},"obj":"Sentence"},{"id":"T2","span":{"begin":128,"end":288},"obj":"Sentence"},{"id":"T3","span":{"begin":289,"end":450},"obj":"Sentence"},{"id":"T4","span":{"begin":451,"end":684},"obj":"Sentence"},{"id":"T5","span":{"begin":685,"end":817},"obj":"Sentence"},{"id":"T6","span":{"begin":818,"end":1052},"obj":"Sentence"},{"id":"T7","span":{"begin":1053,"end":1274},"obj":"Sentence"}],"attributes":[{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"},{"subj":"T1","pred":"source","obj":"Inflammaging"},{"subj":"T2","pred":"source","obj":"Inflammaging"},{"subj":"T3","pred":"source","obj":"Inflammaging"},{"subj":"T4","pred":"source","obj":"Inflammaging"},{"subj":"T5","pred":"source","obj":"Inflammaging"},{"subj":"T6","pred":"source","obj":"Inflammaging"},{"subj":"T7","pred":"source","obj":"Inflammaging"}]},{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":108,"end":126},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":907,"end":923},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":937,"end":956},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":993,"end":1011},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":1025,"end":1051},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0005101"},{"id":"A2","pred":"mondo_id","subj":"T1","obj":"0009960"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0000605"},{"id":"A4","pred":"mondo_id","subj":"T3","obj":"0005271"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0004980"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0005101"},{"id":"A7","pred":"mondo_id","subj":"T6","obj":"0009960"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"0005265"},{"subj":"T1","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T3","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T5","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T6","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T8","pred":"source","obj":"PMID_GLOBAL"}]},{"project":"Anatomy-MAT","denotations":[{"id":"T1","span":{"begin":594,"end":605},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"mat_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MAT_0000084"},{"subj":"T1","pred":"source","obj":"Anatomy-MAT"}]},{"project":"Anatomy-UBERON","denotations":[{"id":"T1","span":{"begin":425,"end":435},"obj":"Body_part"},{"id":"T2","span":{"begin":575,"end":583},"obj":"Body_part"},{"id":"T4","span":{"begin":594,"end":605},"obj":"Body_part"},{"id":"T5","span":{"begin":614,"end":624},"obj":"Body_part"},{"id":"T6","span":{"begin":653,"end":661},"obj":"Body_part"},{"id":"T8","span":{"begin":775,"end":786},"obj":"Body_part"},{"id":"T9","span":{"begin":788,"end":799},"obj":"Body_part"},{"id":"T10","span":{"begin":805,"end":816},"obj":"Body_part"},{"id":"T11","span":{"begin":1038,"end":1043},"obj":"Body_part"},{"id":"T12","span":{"begin":1182,"end":1192},"obj":"Body_part"}],"attributes":[{"id":"A1","pred":"uberon_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL_0000738"},{"id":"A2","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL_0000576"},{"id":"A3","pred":"uberon_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL_0001054"},{"id":"A4","pred":"uberon_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/UBERON_0002371"},{"id":"A5","pred":"uberon_id","subj":"T5","obj":"http://purl.obolibrary.org/obo/CL_0000235"},{"id":"A6","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL_0000576"},{"id":"A7","pred":"uberon_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL_0001054"},{"id":"A8","pred":"uberon_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/CL_0000775"},{"id":"A9","pred":"uberon_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CL_0000542"},{"id":"A10","pred":"uberon_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/CL_0000235"},{"id":"A11","pred":"uberon_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/UBERON_0000160"},{"id":"A12","pred":"uberon_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/CL_0000738"},{"subj":"T1","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T2","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T4","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T5","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T6","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T8","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T9","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T10","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T11","pred":"source","obj":"Anatomy-UBERON"},{"subj":"T12","pred":"source","obj":"Anatomy-UBERON"}]},{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":108,"end":126},"obj":"Phenotype"},{"id":"T2","span":{"begin":907,"end":923},"obj":"Phenotype"},{"id":"T3","span":{"begin":946,"end":956},"obj":"Phenotype"},{"id":"T4","span":{"begin":993,"end":1011},"obj":"Phenotype"},{"id":"T5","span":{"begin":1025,"end":1051},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0100279"},{"id":"A2","pred":"hp_id","subj":"T2","obj":"HP:0041092"},{"id":"A3","pred":"hp_id","subj":"T3","obj":"HP:0011123"},{"id":"A4","pred":"hp_id","subj":"T4","obj":"HP:0100279"},{"id":"A5","pred":"hp_id","subj":"T5","obj":"HP:0002037"},{"subj":"T1","pred":"source","obj":"HP-phenotype"},{"subj":"T2","pred":"source","obj":"HP-phenotype"},{"subj":"T3","pred":"source","obj":"HP-phenotype"},{"subj":"T4","pred":"source","obj":"HP-phenotype"},{"subj":"T5","pred":"source","obj":"HP-phenotype"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}]},{"project":"CL-cell","denotations":[{"id":"T1","span":{"begin":425,"end":435},"obj":"Cell"},{"id":"T2","span":{"begin":575,"end":583},"obj":"Cell"},{"id":"T4","span":{"begin":614,"end":624},"obj":"Cell"},{"id":"T6","span":{"begin":653,"end":661},"obj":"Cell"},{"id":"T8","span":{"begin":775,"end":786},"obj":"Cell"},{"id":"T9","span":{"begin":788,"end":799},"obj":"Cell"},{"id":"T10","span":{"begin":805,"end":816},"obj":"Cell"},{"id":"T12","span":{"begin":1182,"end":1192},"obj":"Cell"}],"attributes":[{"id":"A1","pred":"cl_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/CL:0000738"},{"id":"A2","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0000576"},{"id":"A3","pred":"cl_id","subj":"T2","obj":"http://purl.obolibrary.org/obo/CL:0001054"},{"id":"A4","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0000235"},{"id":"A5","pred":"cl_id","subj":"T4","obj":"http://purl.obolibrary.org/obo/CL:0000394"},{"id":"A6","pred":"cl_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL:0000576"},{"id":"A7","pred":"cl_id","subj":"T6","obj":"http://purl.obolibrary.org/obo/CL:0001054"},{"id":"A8","pred":"cl_id","subj":"T8","obj":"http://purl.obolibrary.org/obo/CL:0000775"},{"id":"A9","pred":"cl_id","subj":"T9","obj":"http://purl.obolibrary.org/obo/CL:0000542"},{"id":"A10","pred":"cl_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/CL:0000235"},{"id":"A11","pred":"cl_id","subj":"T10","obj":"http://purl.obolibrary.org/obo/CL:0000394"},{"id":"A12","pred":"cl_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/CL:0000738"},{"subj":"T1","pred":"source","obj":"CL-cell"},{"subj":"T2","pred":"source","obj":"CL-cell"},{"subj":"T4","pred":"source","obj":"CL-cell"},{"subj":"T6","pred":"source","obj":"CL-cell"},{"subj":"T8","pred":"source","obj":"CL-cell"},{"subj":"T9","pred":"source","obj":"CL-cell"},{"subj":"T10","pred":"source","obj":"CL-cell"},{"subj":"T12","pred":"source","obj":"CL-cell"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"sentences","color":"#ece393","default":true},{"id":"NCBITAXON","color":"#c993ec"},{"id":"mondo_disease","color":"#93ecaf"},{"id":"Glycosmos6-MAT","color":"#ec9493"},{"id":"Inflammaging","color":"#93abec"},{"id":"PMID_GLOBAL","color":"#c5ec93"},{"id":"Anatomy-MAT","color":"#ec93df"},{"id":"Anatomy-UBERON","color":"#93ecdf"},{"id":"HP-phenotype","color":"#ecc593"},{"id":"CL-cell","color":"#ab93ec"}]}]}}