Role of the Leukotriene E4 Receptor GPR99 in Asthma
Technical Report,15 Sep 2017,14 Sep 2018
Brigham and Womens Hospital, Inc. Boston United States
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Cysteinyl leukotrienes cys-LTs, leukotriene C4 LTC4, LTD4, and LTE4, are proinflammatory lipid mediators, and LTE4 acts on the CysLT3R also known as GPR99 to elicit vascular permeability in the skin. We previously demonstrated that GPR99 is expressed on nasal mucosal epithelial cells and mediates mucin release in response to the mold allergen Alternaria and recently found that LTE4GPR99 promotes type 2 inflammation through the activation and expansion of lung brush cells in response to Alternaria. During the first research period, we have developed an in vitro system for testing brush cell function. We cultured mouse tracheal epithelial cells at air-liquid interface for 7 days and added LTE4 to the culture media every other day for a week. DCLK1 staining showed an increased number of brush cells at day 7 after LTE4 treatment. Brush cells were approximately 2-3 percent of all epithelial cells. Stimulation of day 10 mouse tracheal epithelial cell cultures with the mold allergen Alternaria induced cys-LT generation, indicating that the biosynthetic pathway is active. In addition, we find that LTE4 can drive upregulation of brush cell-related genes and brush cell number in air-liquid interface cultures from two different human epithelial cell lines.
- Medicine and Medical Research