Faculty Collaboration Database

Extracellular cathepsin K exerts antimicrobial activity and is protective against chronic intestinal inflammation in mice. Gut 2013 Apr;62(4):520-30

Date

03/24/2012

Pubmed ID

22442160

DOI

10.1136/gutjnl-2011-300076

Scopus ID

2-s2.0-84874661796 (requires institutional sign-in at Scopus site)   37 Citations

Abstract

OBJECTIVE: Cathepsin K is a lysosomal cysteine protease that has pleiotropic roles in bone resorption, arthritis, atherosclerosis, blood pressure regulation, obesity and cancer. Recently, it was demonstrated that cathepsin K-deficient (Ctsk(-/-) ) mice are less susceptible to experimental autoimmune arthritis and encephalomyelitis, which implies a functional role for cathepsin K in chronic inflammatory responses. Here, the authors address the relevance of cathepsin K in the intestinal immune response during chronic intestinal inflammation.

DESIGN: Chronic colitis was induced by administration of 2% dextran sodium sulphate (DSS) in distilled water. Mice were assessed for disease severity, histopathology and endoscopic appearance. Furthermore, DSS-exposed Ctsk(-/-) mice were treated by rectal administration of recombinant cathepsin K. Intestinal microflora was assessed by real-time PCR and 16srDNA molecular fingerprinting of ileal and colonic mucosal and faecal samples.

RESULTS: Using Ctsk(-/-) mice, the authors demonstrate a protective role of cathepsin K against chronic DSS colitis. Dissecting the underlying mechanisms the authors found cathepsin K to be present in intestinal goblet cells and the mucin layer. Furthermore, a direct cathepsin K-mediated bactericidal activity against intestinal bacteria was demonstrated, which potentially explains the alteration of intestinal microbiota observed in Ctsk(-/-) mice. Rectal administration of recombinant cathepsin K in DSS-treated Ctsk(-/-) mice ameliorates the severity of intestinal inflammation.

CONCLUSION: These data identify extracellular cathepsin K as an intestinal antibacterial factor with anti-inflammatory potential and suggest that topical administration of cathepsin K might provide a therapeutic option for patients with inflammatory bowel disease.

Author List

Sina C, Lipinski S, Gavrilova O, Aden K, Rehman A, Till A, Rittger A, Podschun R, Meyer-Hoffert U, Haesler R, Midtling E, Pütsep K, McGuckin MA, Schreiber S, Saftig P, Rosenstiel P

Author

Emilie Regner MD Assistant Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Cathepsin K
Colitis
Dextran Sulfate
Disease Models, Animal
Endoscopy, Gastrointestinal
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Mice
Mice, Inbred C57BL
Real-Time Polymerase Chain Reaction