Diminished levels of nasal S100A7 (psoriasin) in seasonal allergic rhinitis: an effect mediated by Th2 cytokines

Abstract

BackgroundS100A7 is an antimicrobial peptide involved in several inflammatory diseases. The aim of the present study was to explore the expression and regulation of S100A7 in seasonal allergic rhinitis (SAR).MethodsNasal lavage (NAL) fluid was obtained from healthy controls before and after lipopolysaccharide (LPS) provocation, from SAR patients before and after allergen challenge, and from SAR patients having completed allergen-specific immunotherapy (ASIT). Nasal biopsies, nasal epithelial cells and blood were acquired from healthy donors. The airway epithelial cell line FaDu was used for in vitro experiments. Real-time RT-PCR and immunohistochemistry were used to determine S100A7 expression in nasal tissue and cells. Release of S100A7 in NAL and culture supernatants was measured by ELISA. The function of recombinant S100A7 was explored in epithelial cells, neutrophils and peripheral blood mononuclear cells (PBMC).ResultsNasal administration of LPS induced S100A7 release in healthy non-allergic subjects. The level of S100A7 was lower in NAL from SAR patients than from healthy controls, and it was further reduced in the SAR group 6 h post allergen provocation. In contrast, ASIT patients displayed higher levels after completed treatment. S100A7 was expressed in the nasal epithelium and in glands, and it was secreted by cultured epithelial cells. Stimulation with IL-4 and histamine repressed the epithelial S100A7 release. Further, recombinant S100A7 induced activation of neutrophils and PBMC.ConclusionsThe present study shows an epithelial expression and excretion of S100A7 in the nose after microbial stimulation. The levels are diminished in rhinitis patients and in the presence of an allergic cytokine milieu, suggesting that the antimicrobial defense is compromised in patients with SAR.

Upregulated levels of human β‐defensins in patients with seasonal allergic rhinitis after allergen‐specific immunotherapy treatment

“…Further, a deficient HBD expression in the nasal epithelium has a tendency to make individuals more prone to persistent nasal colonization with Staphylococcus aureus . Other AMPs, such as S100A7 (psoriasin), have shown reduced levels in upper airway tissues during infection, chronic rhinosinusitis, and SAR . In line with our finding of reduced mRNA levels of HBD1‐3 in nasal biopsies from patients with SAR, lower levels of HBD1‐4 have been documented in allergic compared to nonallergic mucosa .…”

“…It therefore seems likely that the increased levels of HBDs seen among our SAR patients after ASIT are a result of such cytokine shift. This finding is supported by a recent study reporting lower levels of S100A7 in NAL from SAR patients than from healthy controls, and the restoration of these levels to normal 3 years after completion of ASIT …”

“…Strong evidence points to a role of Th2 cytokines in this process. We have recently shown that interleukin 4 (IL‐4), IL‐5, and histamine downregulate the epithelial release of HBD1‐3 and S100A7 . Likewise, exposure of airway epithelial cells to IL‐4 and IL‐13 has been found to decrease the antimicrobial activity; eg, by suppressing mRNA levels of HBD2 .…”

Barrier function of the nasal mucosa in health and type‐2 biased airway diseases

“…Moreover, while epithelial expression and excretion of S100A7 were observed in the nose after microbial stimulation, the levels are diminished in rhinitis patients and in the presence of an allergic cytokine milieu. All together, these results suggest that the antimicrobial defense by S100A7 is compromised in patients with seasonal allergic rhinitis (Fig. ).…”

Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis

“…Levels of mRNA for S100A7 and S100A8/S100A9 were found to be lower in nasal epithelial cells from CRS patients, and protein was reduced in nasal lavage fluids (54, 94, 95). S100A7 is also lower in lavage fluid from patients with allergic rhinitis (96). The heterodimer of S100A8/S100A9, known as calprotectin, is also expressed by neutrophils and consequently calprotectin levels are highly elevated within sinonasal tissue and polyps due to neutrophil recruitment (95, 97).…”