Evaluation of inflammasome profile in cutaneous lesions of adults with atopic dermatitis

Abstract

Atopic dermatitis (AD) is a recurrent, chronic inflammatory skin disease with intense pruritus and xerosis. The etiopathogenesis of AD is multifactorial, involving genetic, environmental and immunological factors, among others, in addition to the chronic, cutaneous colonization by Staphylococcus aureus (S. aureus) in 80-100% of the patients. It is known that keratinocytes and antigen-presenting cells (APCs) of the skin express pathogen-associated molecular pattern recognition receptors (PRRs). NRLPs (nucleotide-binding oligomerization domain-containing proteins), of the PRR family, respond to various ligands, such as DAMPs, ATP and urate crystals, and exogenous agents such as asbestos and silica. These receptors form a intracellular multiprotein complex, known as inflammasome, which induces the production of IL-1² and IL-18 through the activation of caspase 1. Changes in NLRP1 gene expression are associated with AD severity, and impairment of expression of NLRP3 may partially explain the contribution of S. aureus to chronic inflammation in AD. Recent studies evidence that inflammasomes are activated during S. aureus infection, including NLRP3, via NF-kB, increasing pro- IL-1² transcription, caspase-1 activation and IL-1² secretion, together with IL-18. The objective of this study is to evaluate the possible relationship between inflammasomes and the role of S. aureus in the maintenance of AD inflammation. The following evaluations will be performed: i) Analysis of the expression of inflammasome (NLRP1, NLRP3, AIM2, IL-1², IL-18) in the skin by immunohistochemistry; ii) Analysis of mRNA expression of the components of skin inflammasome in patients with moderate to severe AD and non-atopic controls, by real time PCR; iii) Analysis of the expression of inflammasome in culture supernatants of primary keratinocytes at unstimulated conditions and under staphylococcal enterotoxin B (SEB) stimulation by real time PCR; iiii) Sequencing of miRNAs related to the regulation of inflammasomes in AD skin and controls without AD. These innate immunity parameters, as well as their possible relationship with staphylococcal enterotoxins, may offer a better understanding of the pathogenesis of atopic dermatitis and contribute to the development of future therapeutic targets. (AU)