Simon K. Jackson
Lysophospholipid metabolism facilitates Toll-like receptor 4 membrane translocation to regulate the inflammatory response
Jackson, Simon K.; Abate, Wondwossen; Parton, Joan; Jones, Simon; Harwood, John L.
Authors
Wondwossen Abate
Joan Parton
Simon Jones Simon10.Jones@uwe.ac.uk
Senior Lecturer in Marketing
John L. Harwood
Abstract
Sepsis, an overwhelming inflammatory response to infection, is a major cause of morbidity and mortality worldwide and has no specific therapy. Phospholipid metabolites, such as lysophospholipids, have been shown to regulate inflammatory responses in sepsis, although their mechanism of action is not well understood. The phospholipid-metabolizing enzymes, lysophospholipid acyltransferases, control membrane phospholipid composition, function, and the inflammatory responses innate immune cells. Here, we show that lysophosphatidylcholine acyltransferase (LPCAT) regulates inflammatory responses to LPS and other microbial stimuli. Specific inhibition of LPCAT downregulated inflammatory cytokine production monocytes and epithelial cells by preventing translocation of TLR4 into membrane lipid raft domains. Our observations demonstrate a new regulatory mechanism that facilitates the innate immune responses to microbial molecular patterns and provide a basis for the anti-inflammatory activity observed in many phospholipid metabolites. This provides the possibility of the development new classes of anti-inflammatory and antisepsis agents. © Society for Leukocyte Biology.
Journal Article Type | Article |
---|---|
Publication Date | Jul 1, 2008 |
Journal | Journal of Leukocyte Biology |
Print ISSN | 0741-5400 |
Publisher | Society for Leukocyte Biology |
Peer Reviewed | Peer Reviewed |
Volume | 84 |
Issue | 1 |
Pages | 86-92 |
DOI | https://doi.org/10.1189/jlb.0907601 |
Keywords | lipopolysaccharide, lysophosphatidylcholine acyltransferase, sepsis |
Public URL | https://uwe-repository.worktribe.com/output/1019321 |
Publisher URL | http://dx.doi.org/10.1189/jlb.0907601 |
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