title: Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response.
abstract: 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.
authors: Section of Digestive Diseases and Departments of Pathology and Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
authors: Ahsan F
authors: AF
authors: Malik
authors: Rafaz
authors: R
authors: Hoque
authors: Xinshou
authors: X
authors: Ouyang
authors: Ayaz
authors: A
authors: Ghani
authors: Enping
authors: E
authors: Hong
authors: Khadija
authors: K
authors: Khan
authors: Laura Beth
authors: LB
authors: Moore
authors: Gilbert
authors: G
authors: Ng
authors: Fay
authors: F
authors: Munro
authors: Richard A
authors: RA
authors: Flavell
authors: Yan
authors: Y
authors: Shi
authors: Themis R
authors: TR
authors: Kyriakides
authors: Wajahat Z
authors: WZ
authors: Mehal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D001672:Biocompatible Materials / Q000009:adverse effects*; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism*; D016000:Cluster Analysis; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005549:Foreign-Body Reaction / Q000150:complications / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D015726:Giant Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000150:complications / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D053583:Interleukin-1beta / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D019904:Polymethyl Methacrylate / Q000009:adverse effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D001672:Biocompatible Materials; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; C512299:Ipaf protein, mouse; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; D019904:Polymethyl Methacrylate; D020170:Caspase 1; D001241:Aspirin