Expression of CXC Chemokine Receptors in Acute Ulcerative Colitis: Initial Study from an Animal Model

Abstract

Background:Ulcerative colitis (UC) is an inflammatory disease which is characterized by infiltration of inflammatory cells, crypt abscesses, distortion of the mucosal glands, and goblet cell depletion. The existence of neutrophil-rich inflammation in colon tissues of patients with UC is one of the most significant histological features of this disease. Nonetheless, the expression of CXCR chemokine receptors which appear as the main chemical mediators governing the migration of neutrophils into the mucosal tissue of patients with UC has not been well clarified.Materials and Methods:In this experimental study, the UC model was induced in Wistar rats by administration of 2 ml 4% acetic acid into the large colon through the rectum. Animals were anesthetized after 48 h; their colon tissue samples were isolated for macroscopic and histopathological examination. The expression of receptor1-7 of CXC chemokine was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) technique.Results:Heavy infiltration of neutrophils, coagulative necrosis, and ulcers were observed in H and E staining, which pathologically proved the UC model. qRT-PCR results indicated that CXCR2 as one of the important ELR+ chemokine family receptors bears the highest expression in the UC group (32 fold) than the control group (P ≤ 0.05). In addition, other CXCRs of this group including CXCR1 did not possess any change (P > 0.05). In contrast, RLR negative chemokine family receptors did not show any changes with the normal group.Conclusion:The results showed that CXCR2 is the only receptor for CXCL family which was remarkably upregulated in experimental UC and that CXCR2 might play a significant role in the pathogenesis of UC.

Myeloid cell influx into the colonic epithelium is associated with disease severity and non-response to anti-Tumor Necrosis Factor Therapy in patients with Ulcerative Colitis

“…Furthermore, IL-17/IL-22-stimulated colonic tissues up-regulated key myeloid-recruiting chemokine genes including CXCL1, CXCL2 and CXCL3, providing a mechanistic link between the observed T cell and myeloid cell perturbations in UC. Top drivers of histologic activity in UC were also dominated by myeloid-cell associated genes, including S100A8/S9, FPR1 and FPR2 69 , FCGR3B 70 , CLEC4A, TREM1 39,71 , CXCR1/2 72 and CXCL1. Other notable genes associated with increased histological activity included .…”