The Detergent Effect of Mesalazine Interferes with Phosphatidylcholine Binding to Mucin 2

Stremmel, Wolfgang; Staffer, Simone; Gehrke, Sven G.

doi:10.1159/000493347

Cited by 10 publications

(8 citation statements)

References 19 publications

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“…Accordingly, application of delayed-release lecithin led to an improvement of ulcerative colitis [180]. Yet, simultaneous application of lecithin and the established drug for ulcerative colitis, mesalazine, did not result in the expected efficiency, probably because mesalazine removed mucinbound lecithin [181]. Other ways to reduce penetrability through chemical interactions of UC-mucus are conceivable.…”

Section: Expert Opinionmentioning

confidence: 99%

Microbiota and mucosal defense in IBD: an update

Stange

Schroeder

2019

Expert Review of Gastroenterology & Hepatology

118

104

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Introduction: Inflammatory bowel diseases (IBD) are on the rise worldwide. This review covers the current concepts of the etiology of Crohn´s disease and ulcerative colitis by focusing on an unbalanced interaction between the intestinal microbiota and the mucosal barrier. Understanding these issues is of paramount importance for the development of targeted therapies aiming at the disease cause. Area covered: Gut microbiota alterations and a dysfunctional intestinal mucosa are associated with IBD.Here we focus on specific defense structures of the mucosal barrier, namely antimicrobial peptides and the mucus layer, which keep the gut microbiota at a distance under healthy conditions and are defective in IBD. Expert commentary: The microbiology of both forms of IBD is different but characterized by a reduced bacterial diversity and richness. Abundance of certain bacterial species is altered, and the compositional changes are related to disease activity. In IBD the mucus layer above the epithelium is contaminated by bacteria and the immune reaction is dominated by the antibacterial response. Human genetics suggest that many of the basic deficiencies in the mucosal response, due to Paneth cell, defensin and mucus defects, are primary. Nutrition may also be important but so far there is no therapy targeting the mucosal barrier.

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Section: Expert Opinionmentioning

confidence: 99%

Microbiota and mucosal defense in IBD: an update

Stange

Schroeder

2019

Expert Review of Gastroenterology & Hepatology

118

104

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“…For a translational application, it is necessary to clarify if mucin interferes with this effect on RBD:ACE2 binding. It is known that the mucins can associate with other proteins in a hydrophobic manner [ 60 ]. The experiments revealed that even in the presence of 100 µg/mL of mucin no effect on the inhibitory activity could be determined ( Figure 6 B).…”

Section: Resultsmentioning

confidence: 99%

Morphogenetic (Mucin Expression) as Well as Potential Anti-Corona Viral Activity of the Marine Secondary Metabolite Polyphosphate on A549 Cells

et al. 2020

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The mucus layer of the nasopharynx and bronchial epithelium has a barrier function against inhaled pathogens such as the coronavirus SARS-CoV-2. We recently found that inorganic polyphosphate (polyP), a physiological, metabolic energy (ATP)-providing polymer released from blood platelets, blocks the binding of the receptor binding domain (RBD) to the cellular ACE2 receptor in vitro. PolyP is a marine natural product and is abundantly present in marine bacteria. Now, we have approached the in vivo situation by studying the effect of polyP on the human alveolar basal epithelial A549 cells in a mucus-like mucin environment. These cells express mucins as well as the ectoenzymes alkaline phosphatase (ALP) and adenylate kinase (ADK), which are involved in the extracellular production of ATP from polyP. Mucin, integrated into a collagen-based hydrogel, stimulated cell growth and attachment. The addition of polyP to the hydrogel significantly increased cell attachment and also the expression of the membrane-tethered mucin MUC1 and the secreted mucin MUC5AC. The increased synthesis of MUC1 was also confirmed by immunostaining. This morphogenetic effect of polyP was associated with a rise in extracellular ATP level. We conclude that the nontoxic and non-immunogenic polymer polyP could possibly also exert a protective effect against SARS-CoV-2-cell attachment; first, by stimulating the innate antiviral response by strengthening the mucin barrier with its antimicrobial proteins, and second, by inhibiting virus attachment to the cells, as deduced from the reduction in the strength of binding between the viral RBD and the cellular ACE2 receptor.

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“…Earlier attempts to target mucus by enhancing mucus formation and epithelial energy by supplying additional short chain fatty acids locally were inconclusive (110). Another approach was the oral administration of lecithin to combine with the mucus, but it failed in phase III (111).…”

Section: Targeting Mucusmentioning

confidence: 99%

Current and future aspects of IBD research and treatment: The 2022 perspective

Stange

2022

Front. Gastroenterol.

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Inflammatory bowel diseases (IBD) have seen major progress in current concepts and treatment regimes. Based on the theory of an inadequate “overshoot” of the mucosal immune response to the intestinal microbiome, therapies have been developed to interfere with the key mediators of inflammation from cytokines, including TNF and IL12/23, to integrins such as α4ß7 and intracellular cytokine signal transducers such as janus kinases. Recently, sphingosine-1-receptor agonists were marketed to suppress mucosal inflammation by sequestering lymphocytes in peripheral lymph nodes. However, the aim of these regimes targeting immunity to induce a long-term deep remission, including mucosal healing, is missed in most patients. Contrasting these anti-inflammatory mechanisms of action, the pathogenic focus has finally shifted to the mucosal antibacterial barrier in both Crohn´s disease and ulcerative colitis. Translating this novel concept requires a completely different approach but, in the end, may come closer to a cure of these devastating diseases, in which an incomplete immune modulation fails to achieve the key endpoints: halting disease activity and progression. This review aims to give an overview of past, current, and future concepts in IBD, focusing on both pathogenesis and consequent therapy. A cure is in sight only if both reflect the actual key mechanisms of slow bacterial entry into the mucosa and are harmonized and in line.

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The Detergent Effect of Mesalazine Interferes with Phosphatidylcholine Binding to Mucin 2

Cited by 10 publications

References 19 publications

Microbiota and mucosal defense in IBD: an update

Microbiota and mucosal defense in IBD: an update

Morphogenetic (Mucin Expression) as Well as Potential Anti-Corona Viral Activity of the Marine Secondary Metabolite Polyphosphate on A549 Cells

Current and future aspects of IBD research and treatment: The 2022 perspective

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