Host: The Japanese Pharmacological Society
Name : The 97th Annual Meeting of the Japanese Pharmacological Society
Number : 97
Location : [in Japanese]
Date : December 14, 2023 - December 16, 2023
Itching is the biggest problem for atopic dermatitis (AD) patients. The incidence of AD has been increasing, particularly among young people. Therefore, it is important to clarify the molecular mechanism of itching in AD and to provide a therapeutic agent for itching.
It is known that type 2 inflammation is dominant in the immunological background of AD and that activation of TRP channels, a group of calcium channels, is involved in the transduction of itching as well as that of pain or temperature. It is now widely accepted that cytokines or mediators targeting GPCRs produced in the inflamed sites of AD patients bind to their receptors on sensory neurons followed by activation of TRPA1 and/or TRPV1 transducing the itching signals.
We previously demonstrated that periostin, a matricellular protein, plays an important role in the setting of AD. However, the relationship between periostin and itching had been unclear and no appropriate inhibitor for periostin had been available. We found that mice deleting Ikk2 named FADS mouse show AD-like phenotypes together with severe itching and, moreover, that CP4715, a compound developed as an alphaVbeta3 integrin inhibitor can be an inhibitor against periostin. We investigated the role of periostin on itching in AD using FADS mouse and CP4715 finding that either genetic deficiency of periostin in FADS mice or administration of CP4715 into FADS mice improves itching together with eczema.
Taken together, the periostin/integrin pathway is a novel itching pathway in AD and integrin inhibitors would be promising therapeutic agents for itching in AD.
