The effect of retinoic acid and deoxycholic acid on the differentiation of primary human esophageal keratinocytes.

The mechanism linking gastroduodenal reflux disease to intestinal metaplasia in the esophagus (Barrett's esophagus) has not been determined. Active conjugate metabolites of retinoic acid, in addition to bile acids, undergo an enterohepatic circulation in bile. Retinoic acid and bile acids are candidate mediators of keratinocyte transdifferentiation in Barrett's esophagus. We studied the effects of retinoic acid on the differentiation of primary human esophageal keratinocytes cultured in vitro. Retinoic acid induces expression of a marker of intestinal differentiation, MUC2, in these cells. However, retinoic acid, alone or in combination with the hydrophobic bile acid, deoxycholic acid, does not affect esophageal keratinocyte squamous differentiation as assessed by involucrin expression and cellular morphology. The ability of retinoic acid to induce MUC2 expression may be relevant to the pathogenesis of Barrett's esophagus. However, this does not result in suppression of squamous differentiation.

Endometriosis associated with defective handling of apoptotic cells in the female genital tract is a major cause of autoimmune disease in women.

Several autoimmune diseases are far more common in women than men. The reasons are unknown. Recent studies have shown that many autoimmune diseases which predominantly affect females are characterized by the production of autoantibodies against components of apoptotic cells. Furthermore, in experimental animals, defective clearance of apoptotic cells in a pro-oxidant inflammatory environment can trigger the production of these autoantibodies and related autoimmune disease. Endometriosis is characterized by defective clearance of apoptotic endometrial cells in a pro-oxidant inflammatory environment. It is proposed that this combination of abnormalities triggers autoantibody production in women affected by endometriosis. A proportion of these women will be genetically predisposed to develop overt autoimmune disease. As endometriosis affects at least 4% of the female population of reproductive age, this phenomenon will have a major effect on the gender prevalence of several related autoimmune syndromes. The hypothesis is supported by epidemiological studies which show a strong association between endometriosis and female-predominant autoimmune disorders.

Stem cells of the oesophageal epithelium.

Cancers arising in the oesophageal epithelium are among the most common fatal tumors in the world. Despite this, comparatively little is known about the cell biology and organization of this tissue. Recently, in vitro and in vivo techniques developed over the past 30 years for the study of the epidermis have been applied to the study of the oesophageal epithelium. This approach, combined with data from previous histochemical studies, has lead to the identification and isolation of putative oesophageal epithelial stem cells. Oesophageal epithelial stem cells demonstrate several unusual properties, and their identification may facilitate studies on oesophageal carcinogenesis.