Lysophospholipid acyltransferases in monocyte inflammatory responses and sepsis

Jackson, Simon K.; Parton, Joan

doi:10.1016/j.imbio.2004.04.006

Cited by 10 publications

(9 citation statements)

References 56 publications

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“…Furthermore, our results show that the LPCAT modulation of the inflammatory response is not restricted to the MM6 cell line. This report shows that IL-8 induction from A549 lung epithelial cells is also regulated by inhibition of this enzyme, and previous work showed that IL-6 and TNF-␣ responses from human peripheral blood monocytes were linked to LPCAT activity [8,9].…”

Section: Discussionsupporting

confidence: 71%

“…Previously, it was shown that monocytes and macrophages activated in vivo or in vitro for enhanced inflammatory responses to LPS had altered molecular species of membrane phosphatidylcholine (PC) [6,7]. This led us to identify a phospholipid-modifying enzyme, LPC acyltransferase (LPCAT), which can regulate inflammatory cytokine responses to LPS in monocytes and macrophages [8,9]. Furthermore, we showed that various cytokines including IFN-␥ can up-regulate the activity of LPCAT in innate immune cells [10].…”

Section: Introductionmentioning

confidence: 99%

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Lysophospholipid metabolism facilitates Toll-like receptor 4 membrane translocation to regulate the inflammatory response

Jackson

Abate

Parton

et al. 2008

Journal of Leukocyte Biology

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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 of innate immune cells. Here, we show that lysophosphatidylcholine acyltransferase (LPCAT) regulates inflammatory responses to LPS and other microbial stimuli. Specific inhibition of LPCAT down-regulated inflammatory cytokine production in 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 of new classes of anti-inflammatory and antisepsis agents.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Lysophospholipid metabolism facilitates Toll-like receptor 4 membrane translocation to regulate the inflammatory response

Jackson

Abate

Parton

et al. 2008

Journal of Leukocyte Biology

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“…Phospholipid turnover, known as the Land's cycle [21], has been studied in animals, plants, and fungi [22–24]. It involves deacylation at the sn ‐2 position of phospholipids, followed by reacylation mediated by lysophospholipid acyltransferases such as LPLAT.…”

Section: Discussionmentioning

confidence: 99%

A family of eukaryotic lysophospholipid acyltransferases with broad specificity

et al. 2007

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The budding yeast ALE1 gene encodes a lysophospholipid acyltransferase (LPLAT) with broad specificity. We show that yeast LPLAT (ScLPLAT) belongs to a distinct protein family that includes human MBOAT1, MBOAT2, MBOAT4, and several closely related proteins from other eukaryotes. We further show that two plant proteins within this family, the Arabidopsis proteins AtLPLAT1 and AtLPLAT2, possess lysophospholipid acyltransferase activities similar to ScLPLAT. We propose that other members of this protein family, which we refer to as the LPLAT family, also are likely to possess LPLAT activity. Finally, we show that ScLPLAT differs from the specific lysophosphatidic acid acyltransferase that is encoded by SLC1 in that it cannot efficiently use lysophosphatidic acid produced by acylation of glycerol-3-phosphate in vitro.

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“…In animal cells, it has been shown that this pathway is important for the incorporation of long chain fatty acids (e.g. arachidonic acid) into PC, which is released from PC during inflammatory responses [3].…”

Section: Introductionmentioning

confidence: 99%

The yeast acylglycerol acyltransferase LCA1 is a key component of Lands cycle for phosphatidylcholine turnover

Chen

Kazachkov

Zheng³

et al. 2007

FEBS Letters

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Cellular phospholipids undergo deacylation and reacylation through a process known as Lands cycle. In this report, we provide evidence demonstrating that yeast YOR175c, herein designated as LCA1, encodes a key component of the Lands cycle, the acyl-CoA: lysophosphatidylcholine acyltransferase (LPCAT). Deletion of LCA1 resulted in a drastic reduction in LPCAT activity, while over expression led to a several fold increase in enzyme activity. We further show that disruption of LCA1 caused an enhanced production of glycerophosphorylcholine, a product of phosphatidylcholine (PC) deacylation and that the lysophosphatidic acid acyltransferase SLC1 was not involved in this process. Identification of LCA1 provides an essential molecular tool for further study of Lands cycle in PC turnover.

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Lysophospholipid acyltransferases in monocyte inflammatory responses and sepsis

Cited by 10 publications

References 56 publications

Lysophospholipid metabolism facilitates Toll-like receptor 4 membrane translocation to regulate the inflammatory response

Lysophospholipid metabolism facilitates Toll-like receptor 4 membrane translocation to regulate the inflammatory response

A family of eukaryotic lysophospholipid acyltransferases with broad specificity

The yeast acylglycerol acyltransferase LCA1 is a key component of Lands cycle for phosphatidylcholine turnover

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