Researchers from Kennedy Institute of Rheumatology describe findings in immunology
2007 NOV 20 -- Current study results from the report, 'Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems,' have been published. According to recent research from Hammersmith, the United Kingdom, "TLR3 recognizes double-stranded RNA, a product associated with viral infections. Many details of TLR3-induced mechanisms have emerged from gene-targeted mice or inhibition studies in transformed cell lines." "However, the pathways activated in human immune cells or cells from disease tissue are less well understood. We have investigated TLR3-induced mechanisms of human primary cells of the innate immune system, including dendritic cells (DCs), macrophages (MØs), endothelial cells (ECs), and synovial fibroblasts isolated from rheumatoid arthritis joint tissue (RA-SFs). Here, we report that while these cells all express TLR3, they differ substantially in their response to TLR3 stimulation. The key antiviral response chemokine IP-10 was produced by all cell types, while DCs and MØs failed to produce the proinflammatory cytokines TNF-alpha and IL-6. Unexpectedly, TNF-alpha was found secreted by TLR3-stimulated RA-SF. Furthermore, TLR3 stimulation did not activate NFkappaB, MAPKs, or IRF-3 in DCs and MØs, but was able to do so in ECs and RA-SF. These findings were specific for human cells, thereby revealing a complexity not previously expected," wrote A.M. Lundberg and colleagues, Kennedy Institute of Rheumatology. The researchers concluded: "This is the first report of such cell type-and species-specific response for any TLR stimulation and helps to explain important difficulties in correlating murine models of inflammatory diseases and human inflammation." Lundberg and colleagues published their study in Blood (Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. Blood, 2007;110(9):3245-52). For additional information, contact A.M. Lundberg, Faculty of Medicine, Kennedy Institute of Rheumatology Division, Imperial College of Science, Technology and Medicine, 1 Aspenlea Road, Hammersmith, London, UK. Publisher contact information for the journal Blood is: American Society Hematology, 1900 M Street. NW Suite 200, Washington, DC 20036, USA. Keywords: United Kingdom, Hammersmith, Immunology. This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.
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