PAF and the Digestive Tract. A Review

Izzo, Angelo A.

doi:10.1111/j.2042-7158.1996.tb03903.x

Cited by 19 publications

(12 citation statements)

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“…PAF is a proinflammatory and proliferative factor that can be synthesized rapidly in inflammatory tissues and released into the extracellular environment to trigger biologic effects via specific receptors on the cell membrane (31)(32)(33). Increased PAF levels have been found in ulcerative colitis, necrotizing enterocolitis, and colorectal cancer (31,34). Alk-SMase, by cleaving phosphocholine from PAF, induces inactivation of Figure 7.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Colonic Tumorigenesis in Alkaline Sphingomyelinase (NPP7) Knockout Mice

Chen

Zhang

et al. 2015

Molecular Cancer Therapeutics

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Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor (PAF) and was previously suggested to have anticancer properties. The direct evidence is still lacking. We studied colonic tumorigenesis in alk-SMase knockout (KO) mice. Formation of aberrant crypt foci (ACF) was examined after azoxymethane (AOM) injection. Tumor was induced by AOM alone, a conventional AOM/dextran sulfate sodium (DSS) treatment, and an enhanced AOM/DSS method. b-Catenin was determined by immunohistochemistry, PAF levels by ELISA, and sphingomyelin metabolites by mass spectrometry. Without treatment, spontaneous tumorigenesis was not identified but the intestinal mucosa appeared thicker in KO than in wild-type (WT) littermates. AOM alone induced more ACF in KO mice but no tumors 28 weeks after injection. However, combination of AOM/DSS treatments induced colonic tumors and the incidence was significantly higher in KO than in WT mice. By the enhanced AOM/DSS method, tumor number per mouse increased 4.5 times and tumor size 1.8 times in KO compared with WT mice. Although all tumors were adenomas in WT mice, 32% were adenocarcinomas in KO mice. Compared with WT mice, cytosol expression of b-catenin was significantly increased and nuclear translocation in tumors was more pronounced in KO mice. Lipid analysis showed decreased ceramide in small intestine and increased sphingosine-1-phosphate (S1P) in both small intestine and colon in nontreated KO mice. PAF levels in feces were significantly higher in the KO mice after AOM/DSS treatment. In conclusion, lack of alk-SMase markedly increases AOM/DSS-induced colonic tumorigenesis associated with decreased ceramide and increased S1P and PAF levels.

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Section: Discussionmentioning

confidence: 99%

Enhanced Colonic Tumorigenesis in Alkaline Sphingomyelinase (NPP7) Knockout Mice

Chen

Zhang

et al. 2015

Molecular Cancer Therapeutics

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“…Moreover, we now know that these unique phospholipids may participate in diverse (patho)physiologic events, including cell-cell adhesive interactions, intra-and intercellular signal transduction, cell differentiation, apoptosis, angiogenesis, neurotransmission, reproductive biology, cardiovascular homeostasis, ocular physiology, allergy, gastrointestinal, renal, or pulmonary tissue injury, organ transplantation rejection, and septic shock or systemic inflammatory response syndrome (cf. Zimmerman et al, 1993Zimmerman et al, , 1997Tokumura, 1995;Izzo, 1996;Maclennan et al, 1996;Bazan et al, 1997;Feuerstein et al, 1997;Muzya, 1997, 1998;Mathiak et al, 1997;Muguruma et al, 1997;Prescott, 1997;Tetta et al, 1997;Fink, 1998;Bazan, 1998 chronic inflammation. These inflammatory cells include the PMN, monocyte/macrophage, vascular endothelial cell, lymphocyte, mast cell, basophil, eosinophil, and platelet.…”

Section: (I) Introductionmentioning

confidence: 99%

PAF, a Putative Mediator of Oral Inflammation

McManus

Pinckard

2000

Critical Reviews in Oral Biology & Medicine

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PAF, or platelet-activating factor, is a family of structurally related phospholipids (1 -O-alkyl/acyl/alkenyl-2-acetylsn-glycero-3-phosphocholine) which possesses a wide spectrum of potent pro-inflammatory actions. These phospholipids are synthesized by a diverse array of cells, including neutrophilic polymorphonuclear leukocytes (PMN), platelets, mast cells, monocytes/macrophages, vascular endothelial cells, and lymphocytes. PAF targets these and other cells via specific, G-proteincoupled receptors to initiate intracrine, autocrine, paracrine, and juxtacrine cell activation. Of importance, these unique acetylated phospholipids are frequently synthesized in concert with pro-inflammatory lipid mediators derived from arachidonic acid. Since PAF synergizes with these and other mediators to amplify the inflammatory response, it seems likely that PAF plays an integral, perhaps pivotal, role in acute and chronic inflammatory processes. PAF is present in the mixed saliva of dentate, but not edentulous, human subjects. The levels of PAF in mixed saliva or in gingival crevicular fluid and tissues are significantly increased during oral inflammatory conditions such as periodontitis and mucositis. Interestingly, the levels of salivary PAF correlate with the extent/severity of these oral diseases. These observations suggest that PAF may participate in pathophysiologic events during the course of oral inflammation. The availability of specific PAF receptor antagonists and human recombinant PAF-acetylhydrolase (PAF-AH), a plasma enzyme which rapidly destroys PAF, should provide clinical tools for the investigation of the role of PAF in these and other inflammatory disorders; and perhaps, ultimately, some of these reagents may prove to be therapeutically useful in the treatment and management of these conditions.

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“…A proposed mechanism of action for the effects of Quercetin is a cytoprotective effect mediated by antioxidant properties, stimulation of prostaglandin and inhibition of leukotriene production, events that reinforce the defensive compounds of the gastrointestinal wall (Alarcon de la Lastra et al, 1994;Di Carlo et al, 1999). In a rat model of gastric damage induced by acidified ethanol, the antiulcer effects of flavone, quercetin, naringin, rutin and kaempferol were previously related to the synthesis of platelet activating factor (PAF), a recognized ulcerogenic agent (Izzo, 1996). In this study, intraperitoneal administration of quercetin, rutin and kaempferol reduced tissue erosion in a dose-dependent manner (25-50 mg/kg), while naringin reduced gastric damage only at high dose levels (200-400 mg/kg) and flavone was inactive.…”

Section: Flavonoidsmentioning

confidence: 99%