Lipoxin biosynthesis in inflammatory bowel disease

Mangino, Martin J.; Brounts, Lionel R.; Harms, Bruce; Heise, Charles P.

doi:10.1016/j.prostaglandins.2005.10.004

Cited by 92 publications

(82 citation statements)

References 31 publications

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“…The authors found a reduced ability to form lipoxin A4 after stimulation with a calcium ionophore as compared with un-inflamed colon tissue from healthy controls. 18 These findings are similar to observations that lipoxin-generation capacity is dramatically decreased in peripheral-blood leukocytes from patients with severe asthma. 19 However, the data in the UC study could not distinguish between a general effect of severe inflammation on the generation ability of lipoxin and an effect specific to inflammatory bowel disease.…”

Section: Lipoxins and Resolvins/protectins Control And Resolve Experisupporting

confidence: 88%

Lipoxins and resolvins in inflammatory bowel disease

Weylandt

Kang

Wiedenmann

et al. 2007

Inflammatory Bowel Diseases

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Lipid mediators are important messengers in many physiological processes. The pro-inflammatory effect of many prostaglandins, derived from the essential arachidonic acid, are well established. However, there are also anti-inflammatory lipid mediators: lipoxins and resolvins, derived from essential omega-6 and omega-3 polyunsaturated fatty acids (n-3 and n-6 PUFA), have been shown to control and resolve inflammation in a variety of experimental models of inflammatory disorders. Recent research implicates n-6 PUFA-derived lipoxins and their stable analogues as potent anti-inflammatory compounds in models of inflammatory bowel disease. Similarly, n-3 PUFA-derived lipid mediators such as resolvin E1 were shown to protect from experimental colitis in animal models. Some of their anti-inflammatory effects are mediated by dendritic cells. In this article we discuss the emerging knowledge on the effects of lipoxins and resolvins on various inflammatory pathways and why they are promising candidates for novel therapies of human inflammatory bowel disease.

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Section: Lipoxins and Resolvins/protectins Control And Resolve Experisupporting

confidence: 88%

Lipoxins and resolvins in inflammatory bowel disease

Weylandt

Kang

Wiedenmann

et al. 2007

Inflammatory Bowel Diseases

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“…Mangino et al found a decrease of LX production in colonic mucosal tissue from UC patients, compared with both organ donors and patients affected by slow-transit-time constipation. They found a decrease in epithelial 15-LOX in UC biopsies, suggesting defective biosynthesis of LXs in these patients (160).…”

Section: F Lipoxins and Resolvins: New Drug Candidates For Ibd Treatmentioning

confidence: 93%

Inflammatory Bowel Disease: Mechanisms, Redox Considerations, and Therapeutic Targets

Biasi

Leonarduzzi

Oteiza

et al. 2013

Antioxidants & Redox Signaling

230

145

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Oxidative stress is thought to play a key role in the development of intestinal damage in inflammatory bowel disease (IBD), because of its primary involvement in intestinal cells' aberrant immune and inflammatory responses to dietary antigens and to the commensal bacteria. During the active disease phase, activated leukocytes generate not only a wide spectrum of pro-inflammatory cytokines, but also excess oxidative reactions, which markedly alter the redox equilibrium within the gut mucosa, and maintain inflammation by inducing redoxsensitive signaling pathways and transcription factors. Moreover, several inflammatory molecules generate further oxidation products, leading to a self-sustaining and auto-amplifying vicious circle, which eventually impairs the gut barrier. The current treatment of IBD consists of long-term conventional anti-inflammatory therapy and often leads to drug refractoriness or intolerance, limiting patients' quality of life. Immune modulators or anti-tumor necrosis factor a antibodies have recently been used, but all carry the risk of significant side effects and a poor treatment response. Recent developments in molecular medicine point to the possibility of treating the oxidative stress associated with IBD, by designing a proper supplementation of specific lipids to induce local production of anti-inflammatory derivatives, as well as by developing biological therapies that target selective molecules (i.e., nuclear factor-jB, NADPH oxidase, prohibitins, or inflammasomes) involved in redox signaling. The clinical significance of oxidative stress in IBD is now becoming clear, and may soon lead to important new therapeutic options to lessen intestinal damage in this disease.

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“…LXA 4 and ATL regulate TNF-α-directed neutrophil actions and stimulate IL-4 in exudates, and thus regulate endogenous mediators in the pathogenesis of inflammatory conditions such as periodontal disease (50) In many human diseases, LX production appears to be deficient compared to leukotrienes (Table 2). These include cardiovascular (51), asthma (52), kidney inflammation (53), cystic fibrosis (54), gastrointestinal (55) and periodontal disease (50), to name a few. Designed metabolically stable analogs of LXs and ATLs are useful tools in examining the role(s) and local actions of lipoxins in vivo (Table 2) (56)(57)(58).…”

Section: Lxa 4 and Aspirin-triggered 15-epi-lipoxin A 4 In Animal Modmentioning

confidence: 99%

“…Lipoxins are produced in gut mucosa and serve to limit persistent inflammation (55). Patients with ulcerative colitis have low to absent synthesis of LXA 4 and lower mucosal 15-lipoxygenase-2 enzyme levels (55).…”

Section: Gastrointestinal Disease and Colitismentioning

confidence: 99%

Anti-Inflammatory and Proresolving Lipid Mediators

Serhan

Yacoubian

Rong

2008

Annu. Rev. Pathol. Mech. Dis.

446

380

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The popular view that all lipid mediators are pro-inflammatory arises largely from the finding that non-steroidal anti-inflammatory drugs block the biosynthesis of prostaglandins. The resolution of inflammation was widely held to be a passive event until recently, with the characterization of novel biochemical pathways and lipid-derived mediators that are actively turned on in resolution possessing potent anti-inflammatory and pro-resolving actions. A lipid mediator informatics approach was employed to systematically identify new families of endogenous local-acting mediators from omega-3-polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in resolving exudates in addition to the lipoxins and aspirin-triggered lipoxins generated from arachidonic acid. These new chemical mediator families were coined resolvins and protectins, given their potent bioactions. In this annual review, we present recent advances on the biosynthesis and stereospecific actions of these new pro-resolving mediators, which have also proven to be organ protective and anti-fibrotic.

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Lipoxin biosynthesis in inflammatory bowel disease

Cited by 92 publications

References 31 publications

Lipoxins and resolvins in inflammatory bowel disease

Lipoxins and resolvins in inflammatory bowel disease

Inflammatory Bowel Disease: Mechanisms, Redox Considerations, and Therapeutic Targets

Anti-Inflammatory and Proresolving Lipid Mediators

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