Abstract
BackgroundMycobacterium avium subspecies paratuberculosis (MAP) is suspected to be a causative agent in human Crohn's disease (CD). Recent evidence suggests that pathogenic mycobacteria and MAP can induce the expression of Matrix Metalloproteinases (MMP), which are the main proteases in the pathogenesis of mucosal ulcerations in inflammatory bowel disease (IBD). Within this study we assessed the prevalence of intestinal MAP specific DNA in patients with Crohn's disease, ulcerative colitis (UC), and healthy controls. We further analysed regulation patterns of MMPs in mucosal tissues of UC patients with and without intestinal MAP DNA detection.MethodsColonic biopsy samples were obtained from 63 Norwegian and German IBD patients and 21 healthy controls. RNA was quantified by quantitative real-time polymerase chain reaction (PCR) to study MMP gene expression in both pathological and healthy mucosal specimens. The presence of MAP DNA in colonic mucosa was examined using MAP specific PCR.ResultsMAP DNA was detected in 20% of UC patients and 33% of healthy controls but only in 7% of patients with CD. UC patients treated with corticosteroids exhibited a significantly increased frequency of intestinal MAP DNA compared to those not receiving corticosteroids. Expression of MMP-1, -2, -7, -9, -13, -19, -28 and TNF-α did not differ between UC patients with presence of intestinal MAP DNA compared to those without. MMP-2, MMP-9 and MMP-13 were significantly decreased in UC patients receiving corticosteroids.ConclusionsThe presence of intestinal MAP specific DNA is not associated with altered MMP expression in UC in vivo. Corticosteroids are associated with increased detection of intestinal MAP DNA and decreased expression of certain MMPs. Frequent detection of MAP DNA in healthy controls might be attributable to the wide environmental distribution of MAP and its presence in the food-chain.
Highlights
Mycobacterium avium subspecies paratuberculosis (MAP) is suspected to be a causative agent in human Crohn’s disease (CD)
A total of 63 inflammatory bowel disease (IBD) patients and 21 controls were analysed for the presence of MAP specific DNA in ulcerative colitis (UC) (n = 49) CD (n = 14)
Our results provide evidence that neither expression of MMP1, -2, -7, -9, -13, -19 nor of Matrix Metalloproteinases (MMP)-28 is altered in UC patients with presence of intestinal MAP DNA compared to those without MAP detection
Summary
Mycobacterium avium subspecies paratuberculosis (MAP) is suspected to be a causative agent in human Crohn’s disease (CD). A number of studies and meta-analyses have reported about a more frequent detection of MAP in patients with CD than in controls [4,5,6,7]. It is still a matter of controversy whether MAP represents an etiologic factor for CD or rather a secondary invader of inflamed intestinal mucosa [6,8,9]. In vitro studies have identified increased TNF-a levels in mucosal organ culture supernatants from MAP positive CD patients as well as an increased T-cell proliferation upon incubation of peripheral blood mononuclear cells from CD patients with MAP as pathogenic mechanisms and cellular responses [10,11]
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