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.