Elafin and Its Precursor Trappin-2: What is Their Therapeutic Potential for Intestinal Diseases?

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2022 Nov 10

PMID 36355635

Authors

Celine Deraison

Chrystelle Bonnart

Philippe Langella

Karine Roget

Nathalie Vergnolle

Affiliations

Soon will be listed here.

Abstract

Elafin and its precursor trappin-2 are known for their contribution to the physiological mucosal shield against luminal microbes. Such a contribution seems to be particularly relevant in the gut, where the exposure of host tissues to heavy loads of microbes is constant and contributes to mucosa-associated pathologies. The expression of trappin-2/elafin has been shown to be differentially regulated in diseases associated with gut inflammation. Accumulating evidence has demonstrated the protective effects of trappin-2/elafin in gut intestinal disorders associated with acute or chronic inflammation, or with gluten sensitization disorders. The protective effects of trappin-2/elafin in the gut are discussed in terms of their pleiotropic modes of action: acting as protease inhibitors, transglutaminase substrates, antimicrobial peptides or as a regulator of pro-inflammatory transcription factors. Further, the question of the therapeutic potential of trappin-2/elafin delivery at the intestinal mucosa surface is raised. Whether trappin-2/elafin mucosal delivery should be considered to ensure intestinal tissue repair is also discussed.

Citing Articles

PI3 expression predicts recurrence after chemotherapy with DNA-damaging drugs in gastric cancer.

Harada K, Sakamoto N, Kitaoka T, Nakamura Y, Kondo R, Morisue R J Pathol. 2025; 265(4):472-485.

PMID: 39980125 PMC: 11880974. DOI: 10.1002/path.6400.

Comparative Proteomics Analysis Reveals Distinct Molecular Phenotype and Biomarkers in Patients with Erythrodermic Atopic Dermatitis and Erythrodermic Psoriasis.

Song B, Ning X, Guo L, Liu W, Jin H Inflammation. 2024; 48(1):331-345.

PMID: 38877357 DOI: 10.1007/s10753-024-02078-3.

Expression of Elafin and CD200 as Immune Checkpoint Molecules Involved in Celiac Disease.

Ponce-de-Leon C, Lorite P, Lopez-Casado M, Mora P, Palomeque T, Torres M Int J Mol Sci. 2024; 25(2).

PMID: 38255930 PMC: 10815464. DOI: 10.3390/ijms25020852.

Mucosal expression of PI3, ANXA1, and VDR discriminates Crohn's disease from ulcerative colitis.

James J, Nielsen B, Christensen I, Langholz E, Malham M, Poulsen T Sci Rep. 2023; 13(1):18421.

PMID: 37891214 PMC: 10611705. DOI: 10.1038/s41598-023-45569-3.

Elafin and its precursor trappin-2: What is their therapeutic potential for intestinal diseases?.

Deraison C, Bonnart C, Langella P, Roget K, Vergnolle N Br J Pharmacol. 2022; 180(2):144-160.

PMID: 36355635 PMC: 10098471. DOI: 10.1111/bph.15985.

References

Motta J, Bermudez-Humaran L, Deraison C, Martin L, Rolland C, Rousset P . Food-grade bacteria expressing elafin protect against inflammation and restore colon homeostasis. Sci Transl Med. 2012; 4(158):158ra144. DOI: 10.1126/scitranslmed.3004212. View

Jablaoui A, Kriaa A, Mkaouar H, Akermi N, Soussou S, Wysocka M . Fecal Serine Protease Profiling in Inflammatory Bowel Diseases. Front Cell Infect Microbiol. 2020; 10:21. PMC: 7011180. DOI: 10.3389/fcimb.2020.00021. View

Henriksen P, Hitt M, Xing Z, Wang J, Haslett C, Riemersma R . Adenoviral gene delivery of elafin and secretory leukocyte protease inhibitor attenuates NF-kappa B-dependent inflammatory responses of human endothelial cells and macrophages to atherogenic stimuli. J Immunol. 2004; 172(7):4535-44. DOI: 10.4049/jimmunol.172.7.4535. View

Mihara K, Ramachandran R, Renaux B, Saifeddine M, Hollenberg M . Neutrophil elastase and proteinase-3 trigger G protein-biased signaling through proteinase-activated receptor-1 (PAR1). J Biol Chem. 2013; 288(46):32979-90. PMC: 3829148. DOI: 10.1074/jbc.M113.483123. View

Galipeau H, Wiepjes M, Motta J, Schulz J, Jury J, Natividad J . Novel role of the serine protease inhibitor elafin in gluten-related disorders. Am J Gastroenterol. 2014; 109(5):748-56. PMC: 4219532. DOI: 10.1038/ajg.2014.48. View

Coeshott C, Ohnemus C, Pilyavskaya A, Ross S, Wieczorek M, Kroona H . Converting enzyme-independent release of tumor necrosis factor alpha and IL-1beta from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3. Proc Natl Acad Sci U S A. 1999; 96(11):6261-6. PMC: 26869. DOI: 10.1073/pnas.96.11.6261. View

Motta J, Rolland C, Edir A, Florence A, Sagnat D, Bonnart C . Epithelial production of elastase is increased in inflammatory bowel disease and causes mucosal inflammation. Mucosal Immunol. 2021; 14(3):667-678. PMC: 8075934. DOI: 10.1038/s41385-021-00375-w. View

Oikonomopoulou K, Hansen K, Saifeddine M, Vergnolle N, Tea I, Diamandis E . Proteinase-mediated cell signalling: targeting proteinase-activated receptors (PARs) by kallikreins and more. Biol Chem. 2006; 387(6):677-85. DOI: 10.1515/BC.2006.086. View

Telci D, Griffin M . Tissue transglutaminase (TG2)--a wound response enzyme. Front Biosci. 2005; 11:867-82. DOI: 10.2741/1843. View

10.

Zhang W, Teng G, Wu T, Tian Y, Wang H . Expression and Clinical Significance of Elafin in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2017; 23(12):2134-2141. DOI: 10.1097/MIB.0000000000001252. View

11.

Cenac N, Chin A, Garcia-Villar R, Salvador-Cartier C, Ferrier L, Vergnolle N . PAR2 activation alters colonic paracellular permeability in mice via IFN-gamma-dependent and -independent pathways. J Physiol. 2004; 558(Pt 3):913-25. PMC: 1665017. DOI: 10.1113/jphysiol.2004.061721. View

12.

Bellemare A, Vernoux N, Morin S, Gagne S, Bourbonnais Y . Structural and antimicrobial properties of human pre-elafin/trappin-2 and derived peptides against Pseudomonas aeruginosa. BMC Microbiol. 2010; 10:253. PMC: 2958999. DOI: 10.1186/1471-2180-10-253. View

13.

Wiedow O, Schroder J, Gregory H, Young J, Christophers E . Elafin: an elastase-specific inhibitor of human skin. Purification, characterization, and complete amino acid sequence. J Biol Chem. 1990; 265(25):14791-5. View

14.

Motta J, Wallace J, Buret A, Deraison C, Vergnolle N . Gastrointestinal biofilms in health and disease. Nat Rev Gastroenterol Hepatol. 2021; 18(5):314-334. DOI: 10.1038/s41575-020-00397-y. View

15.

Wang Z, Chen F, Zhai R, Zhang L, Su L, Lin X . Plasma neutrophil elastase and elafin imbalance is associated with acute respiratory distress syndrome (ARDS) development. PLoS One. 2009; 4(2):e4380. PMC: 2633615. DOI: 10.1371/journal.pone.0004380. View

16.

Morand V, Bruneau J, Schoot B, Tagat E, Realo E, Chouaib S . In vitro processing of human tumor necrosis factor-alpha. J Biol Chem. 1995; 270(40):23688-92. DOI: 10.1074/jbc.270.40.23688. View

17.

Vergnolle N . Protease inhibition as new therapeutic strategy for GI diseases. Gut. 2016; 65(7):1215-24. PMC: 4941139. DOI: 10.1136/gutjnl-2015-309147. View

18.

Kuno Y, Ina K, Nishiwaki T, Tsuzuki T, Shimada M, Imada A . Possible involvement of neutrophil elastase in impaired mucosal repair in patients with ulcerative colitis. J Gastroenterol. 2003; 37 Suppl 14:22-32. DOI: 10.1007/BF03326409. View

19.

Pendergraft 3rd W, Rudolph E, Falk R, Jahn J, Grimmler M, Hengst L . Proteinase 3 sidesteps caspases and cleaves p21(Waf1/Cip1/Sdi1) to induce endothelial cell apoptosis. Kidney Int. 2003; 65(1):75-84. DOI: 10.1111/j.1523-1755.2004.00364.x. View

20.

Vergnolle N . Modulation of visceral pain and inflammation by protease-activated receptors. Br J Pharmacol. 2004; 141(8):1264-74. PMC: 1574902. DOI: 10.1038/sj.bjp.0705750. View