Role of microbial toxins in the induction of glucocorticoid receptor beta expression in an explant model of rhinosinusitis.

Abstract

BACKGROUND:

Glucocorticoids (GCs) are the most potent agents currently available for relieving the symptoms of chronic rhinosinusitis. The pathogenesis and molecular basis of GC insensitivity in allergic rhinosinusitis are unknown. Studies done on patients with GC-insensitive asthma demonstrated an overexpression of GC receptor beta (GRbeta), an abnormal splice variant and an endogenous inhibitor of the classic GC receptor alpha. The mechanisms that induce the overexpression of GRbeta remain poorly understood.

OBJECTIVE:

To study the role of Staphylococcus-derived enterotoxin in inducing GRbeta in a human explant model of rhinosinusitis.

METHODS:

Nasal tissue was obtained from inferior turbinates of nonatopic and ragweed-sensitive patients. Tissue samples from nonatopic patients were incubated in the presence and absence of superantigen (SAg) of staphylococcal enterotoxin. In addition, tissue samples from ragweed-sensitive patients were incubated with and without ragweed allergen in the presence or absence of SAg. The expression of GRbeta was assessed by immunocytochemistry using a specific polyclonal antibody to GRbeta.

RESULTS:

SAg increased the expression of GRbeta in both atopic and nonatopic tissue. The highest increase in the expression of GRbeta occurred when atopic nasal tissue was incubated with both ragweed and SAg.

CONCLUSION:

SAg-induced GRbeta is an important modulator of steroid sensitivity in chronic rhinosinusitis.

• Authors: Samer Fakhri, Pota Christodoulopoulos, Meri Tulic, Moto Fukakusa, Saul Frenkiel, Donald Y M Leung, Qutayba A Hamid
• Journal: The Journal of otolaryngology (J Otolaryngol) Vol. 32 Issue 6 Pg. 388-93 (Dec 2003) ISSN: 0381-6605 [Print] Canada
• PMID: 14967085 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Toxins
• Receptors, Glucocorticoid
• Superantigens
• glucocorticoid receptor beta

Topics

• Ambrosia (adverse effects)
• Bacterial Toxins (immunology, pharmacology)
• Case-Control Studies
• Chronic Disease
• Culture Techniques
• Female
• Humans
• Immunohistochemistry
• Male
• Nasal Cavity (drug effects, metabolism, pathology)
• Receptors, Glucocorticoid (biosynthesis, genetics)
• Rhinitis, Allergic, Seasonal (etiology, immunology, metabolism)
• Sinusitis (etiology, immunology, metabolism)
• Staphylococcus (immunology, pathogenicity)
• Superantigens (immunology, pharmacology)