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


METHODS
Nasal 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).


RESULTS
Nasal 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.


CONCLUSIONS
The 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.
Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Huddinge, Sweden. anne.mansson.kvarnhammar@ki.se
Anne Månsson
AM
Kvarnhammar
Camilla
C
Rydberg
Malin
M
Järnkrants
Mia
M
Eriksson
Rolf
R
Uddman
Mikael
M
Benson
Lars-Olaf
LO
Cardell
D000328:Adult; D000485:Allergens; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D003888:Desensitization, Immunologic; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000737:chemistry; D009297:Nasal Mucosa / Q000378:metabolism; D009299:Nasal Provocation Tests; D009504:Neutrophils / Q000187:drug effects; D006255:Rhinitis, Allergic, Seasonal / Q000378:metabolism*; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D018418:Th2 Cells / Q000378:metabolism*; D055815:Young Adult
D000485:Allergens; D016207:Cytokines; C508598:IL4 protein, human; D008070:Lipopolysaccharides; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D015847:Interleukin-4; D006632:Histamine