'Inflammatory bowel disease' (IBD) sounds like a straightforward term - a disease of inflammation in the bowel. However, the history of IBD reveals a story of a nefariously complex set of idiopathic conditions. IBD defies definition, in part because its pathophysiology is not completely understood. For the same reason and despite substantial advances in research, IBD also defies cure. At best, IBD can be defined as a disease of disruption - disrupted physiology, microbiology, immunology and genetics. The term 'IBD' is most often used to describe two separate conditions: ulcerative colitis (UC) and Crohn's disease (CD). This paper reviews the history of IBD, considering the ever-evolving understanding of both UC and CD. Beyond its intrinsic interest, the history of IBD exemplifies a pattern that is becoming increasingly familiar in the 21st century - the story of a chronic, incurable disease that defies the best efforts to treat it.

Professional antigen-presenting cells (APCs) play a crucial role in initiating immune responses. Under pathological conditions, epithelial cells at mucosal surfaces act as nonprofessional APCs, thereby regulating immune responses at the site of exposure. Epithelial cells in the esophagus may contribute to the pathogenesis of eosinophilic esophagitis (EoE) by presenting antigens on the major histocompatibility complex (MHC) class II. Our goal was to demonstrate the ability of esophageal epithelial cells to process and present antigens on the MHC class II system and to investigate the contribution of epithelial cell antigen presentation to EoE. Immunohistochemistry detected HLA-DR, CD80, and CD86 expression and enzyme-linked immunosorbent assay detected interferon-γ (IFNγ) in esophageal biopsies. Antigen presentation was studied using the human esophageal epithelial cell line HET-1A by reverse transcriptase-PCR, flow cytometry, and confocal microscopy. T helper cell lymphocyte proliferation was assessed by flow cytometry and IL-2 secretion. IFNγ and MHC class II were increased in mucosa of patients with EoE. IFNγ increased mRNA of HLA-DP, HLA-DQ, HLA-DR, and CIITA in HET-1A cells. HET-1A engulfed cell debris and processed ovalbumin. HET-1A cells expressed HLA-DR after IFNγ treatment. HET-1A stimulated T helper cell activation. In this study, we demonstrated the ability of esophageal epithelial cells to act as nonprofessional APCs in the presence of IFNγ. Esophageal epithelial cell antigen presentation may contribute to the pathophysiology of eosinophilic esophagitis.

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Background: Oesophagitis is characterised by basal cell hyperplasia and activated eosinophils, which release mediators including major basic protein (MBP). MBP and its mimetic polyarginine activate the calcium sensing receptor (CaSR) on oesophageal epithelium. Fibroblast growth factor 9 (FGF9) is implicated in epithelial homeostasis and proliferative response to injury, but has not been characterised in the oesophagus. Objective: To characterise FGF9 in oesophageal epithelium and oesophagitis, as the result of MBP activation of the CaSR. Methods: Human oesophageal epithelial cells (HET-1A) were used to compare affects of calcium, polyarginine and MBP-peptide on FGF9. HET-1A were transfected with interfering RNA (siRNA CaSR ). FGF9, FGF receptors 2 and 3, bone morphogenetic protein (BMP)-2, BMP-4 and noggin mRNA expression were detected by reverse transcriptase polymerase chain reaction. FGF9 was measured from HET-1A and from normal, gastro-oesophageal reflux and eosinophilic oesophagitis (EoE) patient biopsies using ELISA and immunohistochemistry. HET-1A proliferation was studied using bromodeoxyuridine and MTT. Results: FGF9 was secreted by HET-1A cells treated with polyarginine and MBP-peptide, but not calcium. This effect was abrogated by siRNA CaSR