Squid Ink Polysaccharides inhibit TSLP expression via the Piezo 1-Ca2+-NFAT1 signaling to ameliorate Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a chronic and recurrent inflammatory dermatosis with a growing global prevalence. Its etiopathogenesis involves genetic, immunologic, and environmental factors. Similar to other chronic inflammatory diseases, oxidative stress plays a significant role in its pathogenesis. Squid ink polysaccharides (SIP), the primary components derived from squid ink, have demonstrated beneficial effects in terms of antioxidative properties and immune system enhancement. Nevertheless, the exact impact of SIP on specific cytokines associated with AD remains uncertain. We presented empirical data demonstrating that SIP possesses the capacity to modulate the production of epidermal-barrier-proteins, namely filaggrin (FLG) and involucrin (IVL), within keratinocytes when stimulated by tumor necrosis factor-alpha (TNF-α) and interferon gamma (IFN-γ). Additionally, SIP exhibited noteworthy anti-inflammatory properties on thymic stromal lymphopoietin (TSLP) and interleukin 8 (IL-8). Concurrently, the utilization of SIP exhibited supplementary effectiveness in alleviating AD-like cutaneous symptoms induced by 2,4-dinitrochlorobenzene, encompassing the reinstatement of the epidermal barrier, diminution of immune cell infiltration, and suppression of inflammatory cytokines in murine subjects. These in vivo outcomes were consistent with the observed reduction in TSLP levels, which was accomplished through the Piezo 1-Ca2+-NFAT1 signaling pathway. Considering these cumulative discoveries, SIP emerges as a promising therapeutic contender for the management of AD.