Rats transgenic for HLA-B27 and human beta2microglobulin (B27TR) develop a multisystemic disease resembling inflammatory bowel disease (IBD) and spondyloarthritis. TNFalpha has a crucial role in chronic inflammation. Our objective was to evaluate the effect of anti-TNFalpha treatment on spontaneous IBD in B27TR. Nine-week-old B27TR received monoclonal anti-TNFalpha or an isotypic IgG2a,k up to age of 18 weeks. A second group was monitored up to 18 weeks and then randomly assigned to anti-TNFalpha or IgG2a,k treatment. Each rat was monitored for clinical IBD manifestations. After sacrifice, the colon was examined for pathological changes. TNFalpha receptors (TNF-R1, TNF-R2), Fas/Fas-L expression, and apoptosis were evaluated. IgG2a,k-treated and untreated B27TR presented signs of IBD at 11 weeks, whereas in anti-TNFalpha-treated B27TR no IBD signs were detected. In the late treatment, IBD signs improved after one week. Histopathological analysis of IgG2a,k-treated B27TR colon showed inflammatory signs, that were widely prevented by early treatment. Late treatment did not significantly reduce inflammation. TNF-R1 was weakly expressed in epithelial cells of IgG2a,k-treated B27TR, while it was comparable to controls in anti-TNFalpha-treated. TNF-R2 immunopositivity was strongly evident in IgG2a,k-treated B27TR, whereas was absent in anti-TNFalpha-treated rats. RT-PCR confirmed these results. IgG2a,k-treated B27TR showed, at 18 weeks, few Fas-positive cells and an increase of Fas-L-positive cells. At 27 weeks, Fas-/Fas-L-positive cell number was significantly low. Anti-TNFalpha treatment increased Fas-L expression, whereas Fas increased only with the early treatment. TNFalpha blockade is effective in preventing inflammation in early phase of IBD, maintaining the homeostatic balance of apoptosis.
TNFalpha blockade prevents the development of inflammatory bowel disease in HLA-B27 transgenic rats / A. F., Milia; Manetti, Mirko; Generini, Sergio; L., Polidori; G., Benelli; M., Cinelli; Messerini, Luca; Ibba, Lidia; MATUCCI CERINIC, Marco. - In: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE. - ISSN 1582-1838. - 13:(2009), pp. 164-176. [10.1111/j.1582-4934.2008.00310.x]
TNFalpha blockade prevents the development of inflammatory bowel disease in HLA-B27 transgenic rats
MATUCCI CERINIC, MARCO
2009-01-01
Abstract
Rats transgenic for HLA-B27 and human beta2microglobulin (B27TR) develop a multisystemic disease resembling inflammatory bowel disease (IBD) and spondyloarthritis. TNFalpha has a crucial role in chronic inflammation. Our objective was to evaluate the effect of anti-TNFalpha treatment on spontaneous IBD in B27TR. Nine-week-old B27TR received monoclonal anti-TNFalpha or an isotypic IgG2a,k up to age of 18 weeks. A second group was monitored up to 18 weeks and then randomly assigned to anti-TNFalpha or IgG2a,k treatment. Each rat was monitored for clinical IBD manifestations. After sacrifice, the colon was examined for pathological changes. TNFalpha receptors (TNF-R1, TNF-R2), Fas/Fas-L expression, and apoptosis were evaluated. IgG2a,k-treated and untreated B27TR presented signs of IBD at 11 weeks, whereas in anti-TNFalpha-treated B27TR no IBD signs were detected. In the late treatment, IBD signs improved after one week. Histopathological analysis of IgG2a,k-treated B27TR colon showed inflammatory signs, that were widely prevented by early treatment. Late treatment did not significantly reduce inflammation. TNF-R1 was weakly expressed in epithelial cells of IgG2a,k-treated B27TR, while it was comparable to controls in anti-TNFalpha-treated. TNF-R2 immunopositivity was strongly evident in IgG2a,k-treated B27TR, whereas was absent in anti-TNFalpha-treated rats. RT-PCR confirmed these results. IgG2a,k-treated B27TR showed, at 18 weeks, few Fas-positive cells and an increase of Fas-L-positive cells. At 27 weeks, Fas-/Fas-L-positive cell number was significantly low. Anti-TNFalpha treatment increased Fas-L expression, whereas Fas increased only with the early treatment. TNFalpha blockade is effective in preventing inflammation in early phase of IBD, maintaining the homeostatic balance of apoptosis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.