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Er PA corneal infection. CONCLUSIONS. TREM-2 promoted host resistance to PA Er PA corneal infection. CONCLUSIONS. TREM-2 promoted host resistance to PA infection by suppressing corneal inflammation via activation of the PI3K/Akt pathway. Keywords and phrases: inflammation, cornea, bacteria, cytokinesontact lens usage increases vulnerability to improvement of microbial keratitis, which is connected with vision loss and blindness.1? The microorganism most generally isolated from corneal GS-441524 Technical Information ulcers induced by speak to lens put on is Pseudomonas aeruginosa (PA).4 PA keratitis usually progresses quickly and presents as a suppurative stromal infiltrate with marked mucopurulent exudate.5,six PA infection also leads to complications that consist of inflammatory epithelial edema, stromal infiltration, and corneal ulceration, which can culminate in significant tissue destruction and loss of function.7 Conventional therapies, which include antibiotic treatment, often fail to manage the tissue damage brought on by excessive nearby inflammation, even though viable bacteria are cleared from the cornea.eight Therefore, along with antibiotic therapy, it's also essential to develop new therapeutic modalities to handle the inflammatory response. The host immune response triggered by invading pathogens relies around the innate immune recognition via patternCrecognition receptors (PRRs), for example Toll-like receptors (TLRs).7 Activation of PRRs initiates a variety of inflammatory events, including infiltration of inflammatory cells (e.g., polymorphonuclear neutrophils [PMNs] and monocytes/macrophages),six,9?1 production of Th1-type cytokines (e.g., IFN-c, IL-12, IL-18), Th2-type cytokines (e.g., IL-4, IL-5, IL-10), and proinflammatory cytokines (e.g., TNF-a, macrophage inflammatory protein [MIP]-2, IL-1b).7,12 These PRR-mediated inflammatory responses are important for bacterial clearance; having said that, if uncontrolled, excessive host inflammation also results in immunopathological tissue harm. As a result, it is very important precisely balance pro- and anti-inflammatory responses in ocular immune defense. As a novel PRR family members, triggering receptors expressed on myeloid cells (TREMs) have not too long ago emerged as essential immune regulators.13?five You'll find two big members within the TREM household, TREM-1 and TREM-2, that are mostly expressed on cells derived in the myeloid lineage, for instance macrophagesCopyright 2013 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-TREM-2 in Corneal Inflammation and dendritic cells.16 Our prior study demonstrated that TREM-1 enhances corneal inflammation soon after PA infection by modulating Th1/Th2 responses and TLR signaling.17 On the other hand, practically nothing is identified concerning the function of TREM-2 inside the eye. A preceding study reports that TREM-2 inhibits the inflammatory response by attenuating macrophage activation in response to lipopolysaccharide (LPS) stimulation.18 Overexpression of TREM-2 in microglia reduces the expression of TNF-a and inducible nitric oxide synthase (iNOS) soon after culture of those cells with apoptotic neurons.19 And blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis.20 These studies together suggested that TREM-2 functions as a damaging regulator within the inflammatory response. Though TREM-1 and TREM-2 share the identical adaptor protein, DNAX activation protein 12 (DAP12), their downstream signals are distinct. TREM-1 functions to amplify the TLR responses in monocytes and neutrophils,13 whereas TREM-2 negatively regulates TLR signaling in macrophages and dendritic cells.18,21 Production of in.