Reduction of TLR2 gene expression in allergic and nonallergic rhinitis.
BACKGROUND
Immunomodulators, including toll-like receptors (TLRs) and defensins, produced in response to pathogenic stimuli, can direct the developing immune system toward a T(H)1 nonallergic phenotype. Increased human beta-defensin (HBD) 4 expression is associated with infection.


OBJECTIVE
To determine whether reduced mucosal levels of TLRs and defensins contribute to the inflammation seen in chronic allergic and nonallergic rhinitis.


METHODS
Real-time polymerase chain reaction was used to determine gene expression levels of HBDs 1 through 4 and TLRs 2 and 4. Immunohistochemical analysis was used to study the localization and distribution of protein for alpha-defensins 1 through 3, HBD2, neutrophil elastase, and TLR2 in sections of nasal turbinate tissue from adults with persistent allergic and idiopathic rhinitis, healthy nasal mucosa, and tonsil tissue.


RESULTS
Allergic mucosa showed a significant (P = .02) reduction in TLR2 messenger RNA expression compared with control mucosa and generally reduced expression for TLR4 and HBDs. Although not significant, the nonallergic group also showed reduced expression for TLRs and HBDs. With the exception of HBD4, increased target gene levels were seen in tonsil tissue. Protein expression of HBD2 and TLR2 was localized in lining and submucosal glandular epithelium but insignificant differences were seen for HBDs, TLRs, neutrophils, and a-defensin between the rhinitic and control patient groups.


CONCLUSIONS
Subjects with allergic and nonallergic rhinitis show reduced TLR and HBD gene expression. The significant reduction in TLR2 gene expression in allergic adults supports the concept that increased TLR2 protects against the development of allergy. The low levels of HBD4 detected in both rhinitis groups suggest lack of an underlying infection pathophysiological feature.
Vanhinsbergh
Lewis J
LJ
Division of Pathology, Queen's Medical Centre, Nottingham University Hospitals Trust, Nottingham, England.
Powe
Desmond G
DG
Jones
Nicholas S
NS
D000293:Adolescent; D000328:Adult; D023082:Defensins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012221:Rhinitis, Allergic, Perennial / Q000235:genetics / Q000276:immunology*; D018709:Statistics, Nonparametric; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D023082:Defensins; D012333:RNA, Messenger; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2