A tryptophol-containing emulgel ameliorates imiquimod-induced psoriasis in mice by decreasing the expression of JAK/STAT pathway members

Abstract Psoriasis is a chronic skin inflammatory disease that involves the IL-23/IL-17 axis. The disease is characterized by severe inflammation, prominent epidermal hyperplasia, scaling and erythema. Tryptophol (TOH) is a quorum-sensing molecule that has anti-inflammatory properties. In this study, we demonstrated the ability of a TOH-containing emulgel to alleviate imiquimod (IMQ)-induced psoriasis in mice. The results revealed that the TOH-containing emulgel decreased the pathological score of the psoriasis area and severity index (PASI). Together with the suppression of keratinocyte proliferation and differentiation, the TOH-containing emulgel alleviated hyperkeratosis and downregulated the expression of K10, K6, K16, K17 and involucrin. Moreover, reduced mast cell infiltration was observed, along with the downregulation of ST2 and IL-33 expression in the mouse skin lesions. CD4+ cell infiltration was reduced, and decreased levels of IL-17A and IL-23 in both the serum and psoriatic skin lesions were associated with reduced activation of the JAK2/STAT3 signalling pathway. Additionally, the TOH-containing emulgel suppressed systemic inflammation in the axillary lymph nodes; alleviated IMQ-induced splenomegaly; downregulated the expression of TNFα, IL-1 and IL-6 in the splenic and lymph node tissues; and reduced the serum levels of TNFα and IL-1β. This study revealed that a TOH-containing emulgel attenuates IMQ-induced inflammation in psoriatic mice and presents a novel therapeutic approach for this condition.