Abstract
Yuanyuan Wang, Catherine Lombard, Sultana Monira Hussain, Cheryce Harrison, Samantha Kozica, Sharmayne R. E. Brady, Helena Teede and Flavia M. Cicuttini
Highlights
Our data indicates that the synthesis of cyclooxygenase (COX) and 15-lipoxygenase (15-LOX) metabolites have a temporal regulation in M1 macrophages upon immune stimuli, we did not detect SPM at any time point. Based on these data and reports by other groups persistent Toll like receptors (TLR) stimulation can provide the signal for the initiation of resolution by tissue resident M1 macrophages, resulting in a lipid mediator switch from inflammatory mediators to accumulation of SPM precursors
It has been shown that upon in vitro trauma of cartilage pieces dsDNA is released from chondrocytes. We hypothesise that this released dsDNA can activate nucleotide binding TLRs, triggering an inflammation based cartilage degradation, leading to post-traumatic osteoarthritis
We performed qPCR, Western Blot and NFkB-Reporter-Luciferase-Assay using C28 chondrocytes incubated with isolated ds DNA to detect TLR3 and -9 expression or NFkB activation
Summary
Based on these data and reports by other groups persistent TLR stimulation can provide the signal for the initiation of resolution by tissue resident M1 macrophages, resulting in a lipid mediator switch from inflammatory mediators to accumulation of SPM precursors. Some TLRs are able to bind free nucleic acids and induce downstream inflammatory pathways, mostly based on NFkB activation. It has been shown that upon in vitro trauma of cartilage pieces dsDNA is released from chondrocytes.
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