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Extracellular cathepsin K exerts antimicrobial activity and is protective against chronic intestinal inflammation in mice.

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.

journal_name

Gut

journal_title

Gut

authors

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

doi

10.1136/gutjnl-2011-300076

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

520-30

issue

eissn

0017-5749

issn

1468-3288

pii

gutjnl-2011-300076

journal_volume

pub_type

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Extracellular cathepsin K exerts antimicrobial activity and is protective against chronic intestinal inflammation in mice.