P-glycoprotein, multidrug resistance 1 gene, and Cyclooxygenase 2 expression in cats with inflammatory bowel disease and low grade alimentary lymphoma /

Resumo

Inflammatory bowel disease (IBD) and low grade alimentary lymphoma (LGAL) are common causes of chronic enteropathies in cats. The aetiology of both diseases is unknown though several mechanisms have been proposed. Additionally, progression of IBD to lymphoma has been proposed in cats and humans but no direct link has been established. The multidrug resistance 1 (MDR-1) gene codes for P-glycoprotein (P-gp), an efflux pump membrane protein that actively transports substrates such as bacterial products and drugs from the inside to the outside of cells being likely implicated in the pathogenesis and resistance to treatments of IBD and LGAL. Otherwise, cyclooxygenase 2 (COX-2) is an inducible inflammatory regulator isoform that acts as mediator of pain, modulator of cytokine production, inducer of regulators of angiogenesis, producer of proinflammatory mediators and promoter of tumourigenesis. Lately, COX-2 has been considered a constitutive enzyme in the gastrointestinal tract that acts as part of the mucosal defence mediated by prostaglandins, but its expression is unknown in cats. Therefore, the main aims were to investigate P-gp, Mdr-1 and COX-2 expression in the small animal of cats with IBD and LGAL, and to correlate these expressions with clinical signs and histopathological abnormalities. The first study showed that most of cats with LGAL presented a discontinuous or abnormal P-gp immunoexpression in the intestinal epithelium and marked immunostaining in the lamina propria (LP) compared to cats with IBD, however most of the cats with IBD showed also mild and marked expression in the LP suggesting that P-gp might be implicated in the pathogenesis, severity of disease and type of therapy. In the second study, increased COX-2 intensity at the epithelial cells was observed in cats with IBD and LGAL compared to control group that might be secondary to the inflammatory response or a protective function in the intestinal reparation. Furthermore, COX-2 expression at the LP was presented in only 33% of LGAL cats, thus further investigation of COX-2 expression in feline lymphoma are needed to clarify its importance in pathogenesis, prognostic and response to the therapy. Finally, the last study found that Mdr-1 and Cox-2 gene expressions were higher in cats with LGAL compared to cats with IBD, and control group presented lower level expression of both gene, therefore these genes may be involved in the pathogenesis of IBD and/or LGAL in cats. Further studies are needed with larger number of control cats, patients with IBD classified as food-responsive and steroid-responsive enteropathy, LGAL and other form of AL, and their follow-up to determine the P-gp, Mdr-1 and COX-2 involvement in pathogenesis, resistance to treatment and prognosis in these feline enteropathies.