Sericin coated thin polymeric films reduce keratinocyte proliferation via the mTOR pathway and epidermal inflammation through IL17 signaling in psoriasis rat model

Abstract

Therapeutic treatment forms can play significant roles in resolving psoriatic plaques or promoting wound repair in psoriatic skin. Considering the biocompatibility, mechanical strength, flexibility, and adhesive properties of silk fibroin sheets/films, it is useful to combine them with anti-psoriatic agents and healing stimulants, notably silk sericin. Here, we evaluate the curative properties of sericin-coated thin polymeric films (ScF) fabricated from silk fibroin, using an imiquimod-induced psoriasis rat model. The film biocompatibility and psoriatic wound improvement capacity was assessed. A proteomics study was performed to understand the disease resolving mechanisms. Skin-implantation study exhibited the non-irritation property of ScF films, which alleviate eczema histopathology. Immunohistochemical and gene expression revealed the depletion of β-defensin, caspase-3 and -9, TNF-α, CCL-20, IL-1β, IL-17, TGF-β, and Wnt expressions and S100a14 mRNA level. The proteomics study suggested that ScF diminish keratinocyte proliferation via the mTOR pathway by downregulating mTOR protein, corresponding to the modulation of TNF-α, Wnt, and IL-1β levels, leading to the enhancement of anti-inflammatory environment by IL-17 downregulation. Hematology data demonstrated the safety of using these biomaterials, which provide a potential therapeutic-option for psoriasis treatment due to desirable effects, especially anti-proliferation and anti-inflammation, functioning via the mTOR pathway and control of IL-17 signaling.

Sericin promotes chondrogenic proliferation and differentiation via glycolysis and Smad2/3 TGF-β signaling inductions and alleviates inflammation in three-dimensional models

“…Although studies on the direct effects of sericin treatment specifically on chondrocyte inflammation or OA have been limited. There are many studies of sericin on anti-inflammatory properties in other models 17 , 67 . Sericin-coated film reduced IL-1β and TNF-α levels in rat psoriasis model 67 .…”

“…There are many studies of sericin on anti-inflammatory properties in other models 17 , 67 . Sericin-coated film reduced IL-1β and TNF-α levels in rat psoriasis model 67 . Moreover, sericin downregulated COX-2 , iNOS , IL-1β , IL-6 , IL-18 , CCL2 , and CCL5 gene expressions 17 , 68 .…”

Pivotal Role of mTOR in Non-Skin Manifestations of Psoriasis

“…Aramwit et al conducted a proteomics study suggesting that sericin fibroin (ScF) reduces keratinocyte proliferation via the mTOR pathway by downregulating the mTOR protein. This corresponds to the modulation of TNF-α, Wnt, and IL-1β levels, ultimately promoting an anti-inflammatory environment through IL-17 downregulation [ 31 ].…”

“…Sericin and fibroin, silk proteins extracted from Bombyx mori cocoons , are natural biopolymers with various medicinal properties, particularly renowned for their wound-healing abilities [ 31 ]. Cream-based and polyvinyl alcohol-based formulations of sericin have shown efficacy in the preclinical studies related to psoriasis treatment.…”

“…Cream-based and polyvinyl alcohol-based formulations of sericin have shown efficacy in the preclinical studies related to psoriasis treatment. The primary anti-psoriatic mechanisms of sericin involve inhibiting epidermal cell overgrowth, reducing epidermal inflammation, and restoring epidermal cell homeostasis through immunomodulatory and antioxidative effects [ 31 ].…”