These results suggest that the number of macrophages in the mucos

These results suggest that the number of macrophages in the mucosa of UC patients increases with the chronicity and it is not only related with the severity of damage since both chronic and newly diagnosed patients exhibited a similar histological damage. check details In both groups of patients, a slight increase in the number of CD86+ cells was observed in the damaged area which seems to be the consequence of the increase in the total amount of macrophages since no differences in the proportion CD86+/CD68+ cells were detected between the non-damaged and damaged mucosa. However, a significant increase in both the number of CD206+ cells and the proportion of CD206+/CD68+ macrophages was identified in the damaged mucosa of chronic patients, compared with the non-damaged tissue.

This effect was not observed in the mucosa of newly diagnosed patients which suggests that the number of CD206+ cells in the damaged mucosa increases with the chronicity of the disease. These results seem to be in apparent contradiction with previous studies showing that the percentage of CD206+/CD68+ cells decreases as damage increases [28,29]. In one of those studies comparisons were performed between active and inactive Crohn’s disease patients and in the other one in the same IBD patient, before and after receiving pharmacological treatment. However as far as we know the present study compares for the first time the damaged and non-damaged mucosa of the same patient and reports an increased proportion of CD206+/CD68+ cells in the injured mucosa.

M2 macrophages are related with mucosal healing [28,29] and it has been reported that activation of the canonical Wnt pathway is an injury associated response [8,30�C32] that plays an essential role in the regeneration of the mucosal damage. Of interest, our immunohistochemical studies reveal nuclear ��-catenin and c-Myc immunostaining located at the base of the crypts in the damaged mucosa of UC patients which suggests that Wnt signalling is active. In addition, this pathway seems to be more activated in the damaged than in the non-damaged mucosa since the amount of nuclear ��-catenin bound to Tcf-4 as well as the mRNA expression of Lgr5 and c-Myc were significantly higher in the injured mucosa than in the non-injured mucosa.

Considering that the Wnt- c-Myc pathway plays an essential role in the proliferation of both stem cells and transit-amplifying cells at the base of the crypt [5] our results suggest that this function is enhanced in the damaged mucosa of chronic UC patients in response to epithelial injury. Carfilzomib Furthermore this pathway has been associated with diminished differentiation [6,8] and in transgenic mice that over express a Wnt inhibitor has been reported that, the inhibition of proliferation in crypt regions promotes the expression of AP at the apical domain [4].

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