Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease

Abstract

In the past decades, continuous effort has been paid to deeply understanding the pathophysiology of inflammatory bowel diseases (IBD), such as ulcerative colitis or Crohn's disease. As the disease typically arises as chronic inflammation of the gastrointestinal mucosa, research has been focused on how such an uncontrolled, deleterious immune response may arise and persist in a certain cohort of patients. Based on those immunologic analyses, the establishment of anti-TNF-a therapy, and the following series of biologic agents achieved great success and dramatically changed the therapeutic strategy of IBD patients. However, to guarantee long-term remission of the disease, the therapeutic standard has been raised to achieve ''mucosal healing'', which requires complete repair of the gastrointestinal mucosa. Recent studies have revealed the unexpected importance of epithelial cells in the pathophysiology of IBD. The general barrier function as well as the cell lineage-specific functions have been deeply attributed to the development of chronic intestinal inflammation. Also, the groundbreaking establishment of the in vitro intestinal stem cell culture system has opened up a way of developing stem cell transplantation therapy to treat otherwise refractory ulcers that may persist in IBD patients. In this review, we would like to focus on the role of epithelial cells in the pathophysiology of IBD, and also give a perspective to the upcoming development of regenerative therapies that may become one of the therapeutic choices to achieve mucosal healing in refractory patients of IBD.

PGE2 is a direct and robust mediator of anion/fluid secretion by human intestinal epithelial cells

“…With regard to the pathophysiology of inflammatory diarrhoea, transport of Cl − may represent a partial component, as other factors such as disruption of the mucosal integrity or an increase of exudates arising from the damaged mucosa may also constitute the major components of inflammatory diarrhoea. However, expression of PGE 2 is upregulated in the inflammatory lesions of UC and CD patients, where other inflammatory cytokines are also abundant51. Thus our present results suggest the possibility that the local PGE 2 concentration may determine the local secretory fluid response of IECs without the involvement of other inflammatory cytokines and thereby partially contribute to the pathophysiology of inflammatory diarrhoea.…”

The glial cell-line derived neurotrophic factor: a novel regulator of intestinal barrier function in health and disease

“…However, in recent years the incidence of IBD has increased, as well as the number of patients in whom this therapy fails (24,41). Importantly, it was previously shown that complete regeneration of the intestinal mucosa, called "mucosal healing," predicts long-term remission and clinical improvement of patients suffering from IBD (40).…”

Diagnosis and treatment of microscopic colitis

“…Genetic factors or the involvement of miRNAs have been suggested, but they remain largely controversial [18]. Additionally, epithelial cells may also play a certain role in the pathogenesis of MC, as they have been implicated in the development of intestinal inflammation [19]. LC and CC may arise from a different immunopathologic basis [20], but the clinical manifestation is mostly common, and therefore it is usually difficult to distinguish one from the other [21].…”