Phosphatidylcholine (Lecithin) and the Mucus Layer: Evidence of Therapeutic Efficacy in Ulcerative Colitis?

Stremmel, Wolfgang; Hanemann, Anja; Ehehalt, Robert; Karner, Max; Braun, Annika

doi:10.1159/000320407

Cited by 49 publications

(47 citation statements)

References 64 publications

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“…Defects in mucin produc tion are well known in patients with ulcerative colitis 128 , and so phosphatidylcholine (lecithin) therapy has been tested in patients with promising results in phase II studies 129 . The results of the phase III study in patients with ulcerative colitis are expected in 2017.…”

Section: T Cellmentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

509

403

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Inflammatory bowel diseases (including IBD, exempli fied by Crohn's disease and ulcerative colitis) are chronic relapsing disorders affecting the gastrointestinal tract. IBD has a progressive and destructive nature and, there fore, can cause various complications including steno ses, abscesses, fistulas, extraintestinal manifestations and colitis associated neoplasias and cancer 1,2 . Thus, effective therapeutic approaches are of high clinical rele vance in patients with IBD. This Review summarizes current therapeutic strategies and highlights emerging new treatment approaches for IBD with special refer ence to the proposed molecular mechanisms of action of anti inflammatory drugs. Current IBD therapiesClassic anti-inflammatory drugs. 5 Aminosalicylates (5 ASAs) are important anti inflammatory drugs that are frequently used for anti inflammatory therapy in patients with ulcerative colitis 3 . By contrast, 5 ASA based drugs show little or no efficacy in inducing res olution of clinical symptoms and tissue inflammation in patients with Crohn's disease 4 .5 ASAs are effective for induction and mainten ance of remission in ulcerative colitis and might also reduce the risk of developing colitis associated tumours in these patients 5 . Several mechanisms of action for 5 ASAs have been proposed, including reduction of prostaglandin synthesis via inhibition of cyclooxygenase, suppression of proinflammatory cytokine production and oxygen free radicals, inhib ition of lipoxygenase, blockade of neutrophil chemo taxis and mast cell activation, and impairment of nuclear factor κB activation (NF κB) in immune cells 3 . Moreover, studies in mice revealed that 5 ASA based drugs augment peroxisome proliferator activated receptor γ (PPARγ) expression and promote PPARγ translocation from the cytoplasm to the nucleus where they result in activation of peroxisome proliferator hormone response element driven genes to suppress colitis activity 6,7 .In addition to 5 ASAs, corticosteroids (systemically or topically delivered) have been used for remission induction in ulcerative colitis 2 . Although cortico steroids favour induction of remission in both ulcer ative colitis and Crohn's disease, they are not suitable for mainten ance of remission in IBD 1,2 . Mechanistically, gluco corticoids bind to a specific cytosolic receptor fol lowed by translocation of the complex to the nucleus to either activate or repress gene transcription (via bind ing to DNA corticosteroid response elements) 8,9 . Additionally, the glucocorticoid-receptor complex can inactivate pro inflammatory transcription factors such as NF κB and activator protein 1 (AP1) via proteinprotein inter actions, thereby preventing their activation of inflammatory mediators (for example, leukotrienes and cytokines such as IL 1 and IL 6). REVIEWS© 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

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Section: T Cellmentioning

confidence: 99%

Current and emerging therapeutic targets for IBD

Neurath

2017

Nat Rev Gastroenterol Hepatol

509

403

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“…Induction of HBD2 can be achieved by 1,25-dihydroxyvitamin D 3 as well as, for example, Escherichia coli Nissle 1917 [48,52]. In terms of modulating the mucus layer function the administration of phosphatidylcholine formulations could be promising agents in UC [53,54]. …”

Section: Summary and Future Implicationsmentioning

confidence: 99%

Defective Antibacterial Barrier in Inflammatory Bowel Disease

Klag¹,

Stange²,

Wehkamp³

2013

Dig Dis

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The pathogenesis of inflammatory bowel disease (IBD) is very complex, including a variety of genetic and environmental contributing factors. In this context, over the past few years, a picture of IBD as a primary defect of the innate immune system rather than the adaptive immune system has evolved. The intestinal antimicrobial barrier morphologically consists of a single layer of epithelial cells and the mucus and constitutes the first defense mechanism against the microbial burden of the gut. From a more mechanistic point of view, this barrier additionally depends on a crucial interplay between the mucus and antimicrobial peptides like for instance defensins. Disturbances in this system are in the pathophysiological center stage of IBD genesis and progression. In this article we will give a short overview about some of the key mechanisms in this context with special attention on defensins and the mucus layer.

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“…The occurrence of NEC was related to the defect or damage of this system; exogenous lecithin administration has shown a good effect on ulcerative colitis [4,5]. CDP-choline, an activated form of choline that plays an important role in lecithin synthesis, reduces the production of free fatty acids, increases triglyceride levels, and is commonly used as a metabolic activators of brain cells in clinical practice.…”

Section: (A) the Control Group (×400) (B) Nec Model Group (×400) mentioning

confidence: 99%

“…Phosphatidylcholine, the main lipid of the gastrointestinal mucosal barrier, exerts a protective effect on the mucosa as a hydrophobic intestinal surfactant and regulates the inflammatory signaling system. Moreover, studies have demonstrated that defect or damage of the phospholipid layer causes inflammation and increases susceptibility to NEC [4]. Thus, exogenous phosphatidylcholine may exert a therapeutic effect on NEC.…”

Section: Introductionmentioning

confidence: 99%