Down-regulation of FcεRI expression on mast cells leads anti-allergic effect.

The high-affinity IgE receptor (FcεRI) is essential for Type-I allergic syndromes represented by hay fever, but any anti-allergic drugs targeting FcεRI haven't been approved. We have been engaged in search for the inhibitors against FcεRI expression on the surface of mast cells to develop the anti-allergic drugs based on the novel mechanism. We found pheophorbide a, one of the porphyrin derivatives, from the crude drug "Perillae Herba" as an active principle reducing the FcεRI expression level. Through the structure activity relationship analysis, chlorin e6, also one of the porphyrin derivatives, was revealed to show a little more potent activity than pheophorbide a. Furthermore, also in vivo test, it was clarified that peroral administration of chlorin e6 brought about the down-regulation of FcεRI expression level on the mast cells collected from rats' abdominal cavity. It is notable that chlorin e6 was finally disclosed to reduce the passive cutaneous anaphylaxis (PCA) reaction, often used as an animal model for allergy, through the peroral administration. Thus, we have demonstrated that the suppression of FcεRI level on mast cells leads to alleviation of the allergic symptoms.