Investigators from Germany have revealed the protective role of a protein in inflammatory bowel disease (IBD). The protein, called CD14, could be targeted to treat or prevent this debilitating and even life-threatening disease.
Inflammatory bowel disease (IBD), a group of diseases that involve inflammation of part or all of the digestive tract and predominantly include ulcerative colitis and Crohn disease, is a result of genetic, microbial, and environmental factors. Many genetic loci have been implicated in IBD development in both humans and mouse models. In particular, a gene called Cd14, which encodes the CD14 protein, has been suggested to be a candidate gene for IBD susceptibility.
CD14 is preferentially expressed by monocytes and macrophages. Some other types of cells such as dendritic cells, neutrophils, and epithelial cells can also express the protein. It has two forms, a membrane form and a soluble form. As part of the innate immune system, it functions to enhance activation of cells by bacterial LPS. Evidence shows that CD14 is present at a low level in the uninflamed intestine and is increased in the inflamed intestine. Additioanlly, mice experiments demonstrate the impact of genetics on gut CD14 level.
The new study, led by investigators from Hannover Medical School, University of Veterinary Medicine Hannover, and University of Erlangen-Nürnberg, have uncovered that CD14 has a protective role in the development of IBD by enhancing intestinal barrier function. Findings of their study are described in The American Journal of Pathology.
The team used a mouse-model system for IBD to better elucidate the disease's pathogenesis. Genetic and candidate gene analyses confirmed that Cd14 is a potentially protective candidate gene. Mice lacking CD14 exhibited more severe inflammation in their gut in comparison to the controls. In contrast, increasing CD14 expression strengthened the integrity of the intestinal barrier.
There is a hypothesis that intestinal homeostasis disturbance through intestinal barrier disruption contributes to IBD development. Epithelial barrier function is regulated and maintained by various molecules, such as tight junction (TJ) proteins. Loss of barrier integrity, which can be caused by bacteria, drugs, and toxic chemicals, leads to bacterial invasion and inflammation. Besides, proinflammatory cytokines like TNF-α and IFN-λ also lead to barrier disruption during inflammation.
This work showed that CD14 appears to regulate TJ proteins by reducing proinflammatory cytokine expression. In this way, CD14 helps maintain intestinal barrier function and prevents against intestinal inflammation. These results suggest that CD14 could be targeted to treat or prevent IBD. (Cusabio offers CD14 proteins and antibodies as well as other biomolecules such as Recombinant AGTR1.)
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