Activation of MyD88/IRAK1 axis and downstream proinflammatory signaling in healthy adult and neonatal African American skin.

The increased prevalence of inflammatory skin diseases such as atopic dermatitis, hidradenitis suppurativa, acne, lupus erythematosus in African American (AA) compared to White Non-Hispanic population is well recognized. However, the underlying mechanisms are largely unknown. Here we analyzed proteome in healthy skin biopsies from AA and White Non-Hispanic volunteers using Olink Explore 384 Inflammation biomarker panel. Among proteins with higher expression in AA skin were IRAK1, IL1A, IL4, IL22RA1. It is known that IL1A binding to IL1R1 receptor results in recruitment of signaling adapter MyD88 and IL1R1-associated kinases including IRAK1, a key signal transducer involved in activation of downstream NF-κB and MAPK signaling cascades. We confirmed the increased IRAK1 expression as well as activation of NF-κB and extracellular signal-regulated kinase1/2 signaling in both AA adult and neonatal skin by western blot analysis of relevant proteins (p65/RelA, IKKs, IκBα, extracellular signal-regulated kinase1/2) phosphorylation at specific activating sites. We also confirmed the overexpression of previously reported differentially expressed in AA skin pro-inflammatory genes such as IL1A, TNFα, fold change ER1G in our sets of AA healthy adult and neonatal skin using qRT-PCR. Overall, our study suggests the importance of further analysis of molecular landscape of healthy AA skin to assess how it may contribute to the increased risk of certain inflammatory diseases within the AA population.