Figure 7.

MMP-7 neutralizing antibody mitigates colonic inflammation in rodent models of colitis. For acute model mimicking ulcerative colitis, C57BL/6 mice were given 3% DSS in drinking water for 7 days. MMP-7 neutralizing antibody was administered once daily by i.p. injection. For chronic model mimicking Crohn’s disease, Sprague Dawley rats were treated with intrarectal injection of TNBS (50 mg/kg) 4 times, with intermittent 3-week intervals. MMP-7 neutralizing antibody was i.p. administered on Mondays, Wednesday, and Fridays for a total of 12 weeks. Animals in the control groups received regular drinking water (for acute model) or saline (for chronic model) as well as i.p. injection of respective IgG in saline. Colon tissue was fixed or snap-frozen after permeability assays. Inflammatory cells were evaluated by two independent pathologists. (A) In vivo colonic permeability of DSS mice measured with FITC-dextran at day 7. (B) MPO activities in the DSS mouse colon tissue. (C) RT-qPCR analysis of interleukin 1β (Il1b) mRNA levels in the DSS mouse colon tissue. (D) Numbers of neutrophils stained with H&E in the DSS mouse colons. (E) Numbers of mast cells stained with toluidine blue in the DSS mouse colons. (F) Numbers of eosinophils stained with H&E in the DSS mouse colons. n=4. *p<0.01 vs control (Ctl) group. #p<0.01 vs DSS group. (G) Dosing protocol (top) and H&E staining of the TNBS rat colons (bottom). Black arrow, severely damaged mucosa. (H) Histological colitis score of the rats. (I) Colon lengths of the TNBS rats. (J) In vivo colonic permeability of the TNBS rats. (K) MPO activities in the TNBS rat colons. (L) Il1b mRNA levels in the TNBS rat colons quantitated by RT-qPCR. (M) Immunofluorescence staining of Claudin-7 in colon Swiss roll sections. Nuclear counterstain was done with DAPI. (N) Quantification of Claudin-7 staining intensity, ranging from absent (0) to highest (3). n=5. *p<0.01 vs control (Ctl) group. ^# p<0.01 vs TNBS group.