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Lipoxins: Pro-resolution lipid mediators in intestinal inflammation

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Presentation on theme: "Lipoxins: Pro-resolution lipid mediators in intestinal inflammation"— Presentation transcript:

1 Lipoxins: Pro-resolution lipid mediators in intestinal inflammation
Jason Goh, Catherine Godson, Hugh R. Brady, Padraic MacMathuna  Gastroenterology  Volume 124, Issue 4, Pages (April 2003) DOI: /gast Copyright © 2003 American Gastroenterological Association Terms and Conditions

2 Fig. 1 Arachidonic acid metabolism and generation of lipoxins. The major biosynthetic pathways of lipoxins are catalyzed by the lipoxygenase (LO) enzyme system. LT, leukotriene; LO, lipoxygenase; 15(S)-HETE, 15(S)-hydroxyeicosatetraenoic acid; LX, lipoxin. Gastroenterology  , DOI: ( /gast ) Copyright © 2003 American Gastroenterological Association Terms and Conditions

3 Fig. 2 Stereochemical structures of LXA4, LXB4, ATL, and analogs.
Gastroenterology  , DOI: ( /gast ) Copyright © 2003 American Gastroenterological Association Terms and Conditions

4 Fig. 3 Transcellular biosynthesis of aspirin-triggered lipoxins (ATL). Acetylation of endothelial cell cyclooxygenase (COX)-2 by aspirin inhibits prostaglandin (PGs) generation and triggers the formation of 15-epimers of lipoxins (ATL) during interaction between neutrophils and vascular endothelium. 15(R)-HETE, 15-(R)-hydroxyeicosatetraenoic acid. Gastroenterology  , DOI: ( /gast ) Copyright © 2003 American Gastroenterological Association Terms and Conditions

5 Fig. 4 Schematic representation of a crypt abscess at the center of intestinal inflammation and hypothetical targets for the induction of a “resolution phenotype” by lipoxins. Generated locally during inflammation via transcellular interaction, LX act rapidly on receptor (R = ALXR) expressed on the basolateral membrane of enterocytes close to the paracellular space. The open and solid arrows emanating from lipoxin indicate inhibitory and stimulatory actions, respectively. LX may limit neutrophil-induced damage by inhibiting their transendothelial and transepithelial adhesion and migration, reducing chemotactic signals, and inhibiting neutrophil activation. LX may antagonize many of the proinflammatory effects of tumor necrosis factor (TNF)-α and down-regulate the induction of many other genes regulated by NF-κB. LX may also be cytoprotective for enterocytes and inhibit chemokine synthesis. To further promote resolution of inflammation, LX may stimulate recruitment of monocytes from the circulation and promote macrophage phagocytosis of apoptotic neutrophils (represented by star-shaped cell). A, apoptotic neutrophil; M, macrophange; R, lipoxin receptor. Nucleated cells in grayscale represent enterocytes and horseshoe-shaped cells represent goblet cells. Gastroenterology  , DOI: ( /gast ) Copyright © 2003 American Gastroenterological Association Terms and Conditions


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