Toll-like receptor 2 agonist Pam3CSK4 up-regulates FcεRI receptor expression on monocytes from patients with severe extrinsic atopic dermatitis

BackgroundBoth microbial antigens and allergens are important factors that can trigger atopic dermatitis (AD). Monocytes from patients with AD have been found to express increased and sustained levels of high-affinity IgE receptor (Fc epsilon RI) and Toll-like receptor 2 (TLR2). We hypothesized that putative interactions exist between TLR2 and Fc epsilon RI on monocytes in the pathogenesis of AD. ObjectiveThis study aimed to understand whether activation of TLR2 by Pam3CSK4 would influence the expression of Fc epsilon RI, and whether mitogen-activated protein kinase (MAPK) signalling pathways were involved in such regulation. MethodsPeripheral blood monocytes from patients with severe extrinsic AD or healthy control patients were treated with the TLR2 agonist Pam3CSK4. The expression of Fc epsilon RI, intracellular TNF- and MAPK family members were analysed by real-time quantitative PCR, flow cytometry and western blotting. ResultsMonocytes from patients with severe extrinsic AD expressed higher levels of surface Fc epsilon RI than were found in monocytes from healthy controls. Stimulation of human monocytes from patients with Pam3CSK4, but not lipopolysaccharide (LPS), resulted in the up-regulation of surface Fc epsilon RI expression by inducing p38 phosphorylation. Pretreatment with a specific inhibitor of p38 kinase inhibited the Pam3CSK4-induced up-regulation of Fc epsilon RI, suggesting the involvement of the p38 pathway in the regulation of this process. ConclusionOur findings indicated interactions between TLR2 and Fc epsilon RI occurred via the activation of p38 in patients with severe extrinsic AD, which might indicate insights into understanding the mechanisms of how bacterial infection can exacerbate the clinical features of AD.