AIM: To investigate the level of mucosal expression and the involvement of the receptor for the advanced glycation end products (RAGE) in delayed apoptosis and tumor necrosis factor (TNF)-α production in Crohn's disease (CD). METHODS: Surgical and endoscopic specimens from both inflamed and non-inflamed areas of the ileum and/or colon were collected from 20 and 14 adult CD patients, respectively, and used for the assessment of RAGE expression by means of immunohistochemistry and western blotting analysis. Normal tissues from 21 control subjects were used for comparison. The same polyclonal anti-human RAGE antibody (R and D System) was used in all experimental conditions. RAGE staining was quantized by a score including both the amount of positive cells and intensity of immunoreactivity; cellular pattern was also described. The effects of RAGE blocking on apoptotic rate and TNF-α production were investigated on immune cells freshly isolated from CD mucosa and incubated both with and without the muramyl dipeptide used as antigenic stimulus. Statistical analysis was performed via the test for trend, with regression models to account for intra-patient correlations. A 2-sided P < 0.05 was considered significant. RESULTS: In inflamed areas, RAGE expression in both the epithelial and lamina propria compartments was higher than control tissues (P = 0.001 and 0.021, respectively), and a cluster of positive cells were usually found in proximity of ulcerative lesions. Similar results were obtained in the lamina propria compartment of non-inflamed areas (P = 0.025). The pattern of staining was membranous and granular cytosolic at the epithelial level, while in the lamina propria it was diffuse cytosolic. When evaluating the amount of protein expression by immunoblotting, a significant increase of both surface area and band intensity (P < 0.0001 for both) was observed in CD inflamed areas compared to control tissue, while in non-inflamed areas a significant increase was found only for band intensity (P < 0.005). Moreover, a significantly lower expression in non-inflamed areas in comparison with inflamed areas was found for both surface area and band intensity (P < 0.0006 for both). Finally, RAGE blocking largely affects both the apoptotic rate of mucosal cells (towards an increase in both non-inflamed and inflamed areas of P < 0.001 and < 0.0001, respectively) and TNF-α secretion (towards a decrease in both non-inflamed and inflamed areas of P < 0.05 and < 0.01, respectively), mainly in the presence of antigenic stimulation. CONCLUSION: RAGE is up-regulated in CD, especially in inflamed areas, and it appears to play a role in the mechanisms involved in chronic inflammation.
AIM: To investigate the level of mucosal expression and the involvement of the receptor for the advanced glycation end products (RAGE) in delayed apoptosis and tumor necrosis factor (TNF)-α production in Crohn's disease (CD). METHODS: Surgical and endoscopic specimens from both inflamed and non-inflamed areas of the ileum and/or colon were collected from 20 and 14 adult CD patients, respectively, and used for the assessment of RAGE expression by means of immunohistochemistry and western blotting analysis. Normal tissues from 21 control subjects were used for comparison. The same polyclonal anti-humanRAGE antibody (R and D System) was used in all experimental conditions. RAGE staining was quantized by a score including both the amount of positive cells and intensity of immunoreactivity; cellular pattern was also described. The effects of RAGE blocking on apoptotic rate and TNF-α production were investigated on immune cells freshly isolated from CD mucosa and incubated both with and without the muramyl dipeptide used as antigenic stimulus. Statistical analysis was performed via the test for trend, with regression models to account for intra-patient correlations. A 2-sided P < 0.05 was considered significant. RESULTS: In inflamed areas, RAGE expression in both the epithelial and lamina propria compartments was higher than control tissues (P = 0.001 and 0.021, respectively), and a cluster of positive cells were usually found in proximity of ulcerative lesions. Similar results were obtained in the lamina propria compartment of non-inflamed areas (P = 0.025). The pattern of staining was membranous and granular cytosolic at the epithelial level, while in the lamina propria it was diffuse cytosolic. When evaluating the amount of protein expression by immunoblotting, a significant increase of both surface area and band intensity (P < 0.0001 for both) was observed in CD inflamed areas compared to control tissue, while in non-inflamed areas a significant increase was found only for band intensity (P < 0.005). Moreover, a significantly lower expression in non-inflamed areas in comparison with inflamed areas was found for both surface area and band intensity (P < 0.0006 for both). Finally, RAGE blocking largely affects both the apoptotic rate of mucosal cells (towards an increase in both non-inflamed and inflamed areas of P < 0.001 and < 0.0001, respectively) and TNF-α secretion (towards a decrease in both non-inflamed and inflamed areas of P < 0.05 and < 0.01, respectively), mainly in the presence of antigenic stimulation. CONCLUSION:RAGE is up-regulated in CD, especially in inflamed areas, and it appears to play a role in the mechanisms involved in chronic inflammation.
Authors: Rebeca Santaolalla; Josep Mañé; Elisabet Pedrosa; Violeta Lorén; Fernando Fernández-Bañares; Josefa Mallolas; Anna Carrasco; Antonio Salas; Mercè Rosinach; Montserrat Forné; Jorge C Espinós; Carme Loras; Michael Donovan; Pere Puig; Miriam Mañosa; Miquel A Gassull; Josep M Viver; Maria Esteve Journal: Inflamm Bowel Dis Date: 2010-11-08 Impact factor: 5.325
Authors: Louis J Sparvero; Denise Asafu-Adjei; Rui Kang; Daolin Tang; Neilay Amin; Jaehyun Im; Ronnye Rutledge; Brenda Lin; Andrew A Amoscato; Herbert J Zeh; Michael T Lotze Journal: J Transl Med Date: 2009-03-17 Impact factor: 5.531
Authors: Angela Isabel Cabrera-García; Jan S Suchodolski; Jörg M Steiner; Romy M Heilmann Journal: J Vet Diagn Invest Date: 2020-07-27 Impact factor: 1.279
Authors: Jay V Patankar; Tanja M Müller; Srinivas Kantham; Miguel Gonzalez Acera; Fabrizio Mascia; Kristina Scheibe; Mousumi Mahapatro; Christina Heichler; Yuqiang Yu; Wei Li; Barbara Ruder; Claudia Günther; Moritz Leppkes; Mano J Mathew; Stefan Wirtz; Clemens Neufert; Anja A Kühl; Jay Paquette; Kevan Jacobson; Raja Atreya; Sebastian Zundler; Markus F Neurath; Robert N Young; Christoph Becker Journal: Nat Cell Biol Date: 2021-07-08 Impact factor: 28.824
Authors: Deiziane V S Costa; Ana C Bon-Frauches; Angeline M H P Silva; Roberto C P Lima-Júnior; Conceição S Martins; Renata F C Leitão; Gutierrez B Freitas; Patricia Castelucci; David T Bolick; Richard L Guerrant; Cirle A Warren; Vivaldo Moura-Neto; Gerly A C Brito Journal: Sci Rep Date: 2019-01-24 Impact factor: 4.379