P-glycoprotein multidrug transporter in inflammatory bowel diseases: More questions than answers.
The gastrointestinal barrier is constantly exposed to numerous environmental substrates that are foreign and potentially harmful. These xenobiotics can cause shifts in the intestinal microbiota composition, affect mucosal immune responses, disturb tissue integrity and impair regeneration. The multidrug transporterABCB1/MDR1p-glycoprotein (p-gp) plays a key role at the front line of host defence by efficiently protecting the gastrointestinal barrier from xenobiotic accumulation. This Editorial discusses how altered expression and function ofABCB1/MDR1p-gp may contribute to the development and persistence of chronic intestinal inflammation in inflammatory bowel diseases (IBD). Recent evidence implies multiple interactions between intestinal microbiota, innate immunity and xenobiotic metabolismviap-gp. While decreased efflux activity may promote disease susceptibility and drug toxicity, increased efflux activity may confer resistance to therapeutic drugs in IBD. Mice deficient in MDR1A develop spontaneously chronic colitis, providing a highly valuable murine IBD model for the study of intestinal epithelial barrier function, immunoregulation, infectious co-triggers and novel therapeutic approaches. Possible associations of humanABCB1gene polymorphisms with IBD susceptibility have been evaluated, but results are inconsistent. Future studies must focus on further elucidation of the pathophysiological relevance and immunological functions of p-gp and how its ambiguous effects could be therapeutically targeted in IBD.
Elke Cario, Experimental Gastroenterology, Department of Gastroenterology and Hepatology, University Hospital Essen, Medical School, University of Duisburg-Essen, 45147 Essen, Germany.
Elke
E
Cario
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D002908:Chronic Disease; D003092:Colitis / Q000235:genetics / Q000378:metabolism; D018432:Drug Resistance, Multiple; D000069196:Gastrointestinal Microbiome; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide; D015262:Xenobiotics / Q000378:metabolism
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015262:Xenobiotics
Inflammatory bowel diseases; Innate immunity; Microbiota; Multidrug resistance; Xenobiotics