METHODS: We performed immunohistochemistry (IHC) to reveal whether GPR41 and GPR43 are present in nasal tissue. To test induction of t-PA, primary normal human bronchial epithelial (NHBE) cells were stimulated with SCFAs. Mediation of responses by SCFA receptors was evaluated by specific receptor gene silencing with siRNA.
RESULTS: IHC study revealed that airway epithelial cells expressed both GPR41 and GPR43 in vitro and in vivo. Propionic acid, butyric acid, and valeric acid strongly induced expression of t-PA mRNA and protein (range X fold to Y fold, p<.05) in NHBE cells. T-PA released into the supernatant was shown to be in the active form. The induction of t-PA by SCFAs was dependent upon both GPR41 and GPR43.
CONCLUSIONS: SCFAs were shown to induce airway epithelial cell expression of t-PA via GPR41 and GPR43. Potent compounds that activate these receptors in vivo may have value by reducing fibrin deposition and shrinking nasal polyps.