Understating the mechanism of IL-33 release in keratinocytes in Atopic dermatitis (AD) in response to Sbi

Abstract

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterised by epidermal barrier dysregulation and type 2 immune response. Staphylococcus aureus (S. aureus) colonises AD skin and induces the release of IL-33. Our study aims to investigate the mechanism of IL-33 release in keratinocytes in response to S. aureus second immunoglobulin (Sbi). Methods: The study investigated the release of IL-33 from normal human epidermal keratinocytes (NHEK) when exposed to second immunoglobulin staphylococcus (Sbi) and assessed it using ELISA. Protein tyrosine Kinase assay and Bioinformatics tools identified immunoglobulin (Ig) containing receptor candidates. The interaction between Sbi and inhibitors in NHEK was also measured through IL-33 ELISA. Additionally, the impact of Ig- containing domain receptor ligands was investigated using a cytokine array. Results: Sbi induced IL-33 release by NHEK after 15 minutes, confirming that Sbi triggers Th2 responses in the skin. Our potential Ig containing receptor candidates are FGFR, PDGFR, and VEGFR. However, our finding indicates that Sbi does not interact with these Ig containing receptors. Additionally, Sbi showed no impact on the production of RTK Ig containing domain receptor ligands in keratinocytes. The Growth factor ligands for the RTK receptors were found in the NHEK supernatant but were not significantly upregulated with Sbi. However, the RTK receptor expression was significantly upregulated when stimulated with Sbi, but the inhibitors did not prevent IL-33 release. The growth factor ligands for the RTK receptors were found. Conclusion: Our study found that Sbi actively stimulates the release of IL-33 from living cells after only 15 minutes. These results strongly suggest that Sbi is a potent stimulator for triggering Th2 responses in the skin. In contrast, the Ig domain-containing receptors (FGFR, VEGFR, PDGFR) appear not to bind with Sbi. Further work is needed to understand the signaling pathway by which Sbi induces the IL-33 release from keratinocytes, which may lead to the development of novel therapy for AD.