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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

Simon K. Jackson simon.jackson@uwe.ac.uk

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
APA6 Citation Jackson, S. K., Abate, W., Parton, J., Jones, S., & Harwood, J. L. (2008). Lysophospholipid metabolism facilitates Toll-like receptor 4 membrane translocation to regulate the inflammatory response. Journal of Leukocyte Biology, 84(1), 86-92. https://doi.org/10.1189/jlb.0907601
DOI https://doi.org/10.1189/jlb.0907601
Keywords lipopolysaccharide, lysophosphatidylcholine acyltransferase, sepsis
Publisher URL http://dx.doi.org/10.1189/jlb.0907601