| Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response. | |
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MedLine Citation:
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PMID: 22109549 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Implantation of biomaterials and devices into soft tissues leads to the development of the foreign body response (FBR), which can interfere with implant function and eventually lead to failure. The FBR consists of overlapping acute and persistent inflammatory phases coupled with collagenous encapsulation and currently there are no therapeutic options. Initiation of the FBR involves macrophage activation, proceeding to giant cell formation, fibroblast activation, and collagen matrix deposition. Despite the recognition of this sequence of events, the molecular pathways required for the FBR have not been elucidated. We have identified that the acute inflammatory response to biomaterials requires nucleotide-binding domain and leucine-rich repeat-containing 3 (Nlrp3), apoptosis-associated speck-like protein containing CARD (Asc), and caspase-1, as well as plasma membrane cholesterol, and Syk signaling. Full development of the FBR is dependent on Asc and caspase-1, but not Nlrp3. The common antiinflammatory drug aspirin can reduce inflammasome activation and significantly reduce the FBR. Taken together, these findings expand the role of the inflammasome from one of sensing damage associated molecular patterns (DAMPs) to sensing all particulate matter irrespective of size. In addition, implication of the inflammasome in biomaterial recognition identifies key pathways, which can be targeted to limit the FBR. |
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Authors:
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Ahsan F Malik; Rafaz Hoque; Xinshou Ouyang; Ayaz Ghani; Enping Hong; Khadija Khan; Laura Beth Moore; Gilbert Ng; Fay Munro; Richard A Flavell; Yan Shi; Themis R Kyriakides; Wajahat Z Mehal |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-11-22 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-14 Completed Date: 2012-02-01 Revised Date: 2012-03-05 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 20095-100 Citation Subset: IM |
Affiliation:
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Section of Digestive Diseases and Departments of Pathology and Biomedical Engineering, Yale University, New Haven, CT 06520, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Animals Apoptosis Regulatory Proteins / metabolism Aspirin / administration & dosage, adverse effects Biocompatible Materials / adverse effects* Calcium-Binding Proteins / metabolism Carrier Proteins / metabolism Caspase 1 / metabolism* Cluster Analysis Cytoskeletal Proteins / metabolism* Foreign-Body Reaction / complications, enzymology, immunology, pathology* Giant Cells / drug effects, immunology, pathology Inflammasomes / metabolism* Inflammation / complications, enzymology, immunology, pathology* Interleukin-1beta / biosynthesis Macrophages, Peritoneal / drug effects, immunology, pathology Membrane Microdomains / drug effects, metabolism Mice Mice, Inbred C57BL Microspheres Polymethyl Methacrylate / adverse effects |
| Grant Support | |
ID/Acronym/Agency:
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1K08DK092281-01/DK/NIDDK NIH HHS; R01 GM072194-01/GM/NIGMS NIH HHS; R01 GM072194-08/GM/NIGMS NIH HHS; R01DK076674-01A2/DK/NIDDK NIH HHS; R21AI089963/AI/NIAID NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Apoptosis Regulatory Proteins; 0/Biocompatible Materials; 0/CIAS1 protein, mouse; 0/Calcium-Binding Proteins; 0/Carrier Proteins; 0/Cytoskeletal Proteins; 0/Inflammasomes; 0/Interleukin-1beta; 0/Ipaf protein, mouse; 0/Pycard protein, mouse; 50-78-2/Aspirin; 9011-14-7/Polymethyl Methacrylate; EC 3.4.22.36/Caspase 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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