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Selective gelatinase inhibition reduces apoptosis and pro-inflammatory immune cell responses in Campylobacter jejuni-infected gnotobiotic IL-10 deficient mice.

Authors :
Alutis ME
Grundmann U
Fischer A
Kühl AA
Bereswill S
Heimesaat MM
Source :
European journal of microbiology & immunology [Eur J Microbiol Immunol (Bp)] 2014 Dec; Vol. 4 (4), pp. 213-22. Date of Electronic Publication: 2014 Dec 16.
Publication Year :
2014

Abstract

Increased levels of the matrix metalloproteinases-2 and -9 (also referred to gelatinase-A and -B, respectively) can be detected in intestinal inflammation. We have recently shown that selective gelatinase blockage by the synthetic compound RO28-2653 ameliorates acute murine ileitis and colitis. We here investigated whether RO28-2653 exerts anti-inflammatory effects in acute Campylobacter jejuni-induced enterocolitis of gnotobiotic IL-10(-/-) mice generated following antibiotic treatment. Mice were perorally infected with C. jejuni (day 0) and either treated with RO28-2653 (75 mg/kg body weight/day) or placebo from day 1 until day 6 post infection (p.i.) by gavage. Irrespective of the treatment, infected mice displayed comparable pathogen loads within the gastrointestinal tract. Following RO28-2653 administration, however, infected mice exhibited less severe symptoms such as bloody diarrhea as compared to placebo controls. Furthermore, less distinct apoptosis but higher numbers of proliferating cells could be detected in the colon of RO28-2653-treated as compared to placebo-treated mice at day 7 p.i. Remarkably, gelatinase blockage resulted in lower numbers of T- and B-lymphocytes as well as macrophages and monocytes in the colonic mucosa of C. jejuni-infected gnotobiotic IL-10(-/-) mice. Taken together, synthetic gelatinase inhibition exerts anti-inflammatory effects in experimental campylobacteriosis.

Details

Language :
English
ISSN :
2062-509X
Volume :
4
Issue :
4
Database :
MEDLINE
Journal :
European journal of microbiology & immunology
Publication Type :
Academic Journal
Accession number :
25544894
Full Text :
https://doi.org/10.1556/EUJMI-D-14-00031