Epidermal growth factor receptor - but not histamine receptor - is upregulated in seasonal allergic rhinitis.
BACKGROUND
We were interested in exploring the molecular mechanisms underlying the observed difference in histamine (H) responsiveness between seasonal allergic rhinitic (SAR) and nonrhinitic (NR) subjects. We hypothesized that SAR subjects express higher nasal mucosal histamine receptor 1 (H1R) and 2 (H2R) levels than do NR subjects. In addition, we examined expression of genes involved in regulating the glandular response, including epidermal growth factor (EGF), EGF receptor (EGFR), and mucins (Muc5Ac and Muc5B).


METHODS
Fourteen subjects, seven SAR and seven NR, were provoked during pollen season with doubling doses of H (0.125-8.0 mg/ml). Nasal airway resistance (NAR) was measured by active posterior rhinomanometry. Provocation was halted when NAR exceeded 150% of baseline. Prior to provocation, nasal scrapings were obtained and mRNA quantified using two-step real-time PCR.


RESULTS
The mean PD50 (concentration of H producing a 50% increase in NAR) was significantly lower in the SAR than NR group (0.36 vs 1.32 mg/ml; P < 0.05). The ratio of relative gene copy numbers between the SAR and NR groups were as follows: H1R, 0.85 (P = 0.52); H2R, 0.67 (P = 0.35); EGF, 1.02 (P = 0.93), and EGFR, 103.5 (P < 0.05).


CONCLUSIONS
There were no significant differences in H1R or H2R mRNA levels between SAR and NR subjects in-season, despite observed differences in H reactivity. SAR subjects, however, did show a significant elevation in EGFR expression, consistent with the observation of mucus hypersecretion in allergic rhinitis.
Matovinovic
E
E
Division of Occupational and Environmental Medicine, University of California, San Francisco, CA, USA.
Solberg
O
O
Shusterman
D
D
D000328:Adult; D000368:Aged; D000403:Airway Resistance; D016022:Case-Control Studies; D004815:Epidermal Growth Factor / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D006632:Histamine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009296:Nasal Cavity / Q000503:physiopathology; D009299:Nasal Provocation Tests; D012333:RNA, Messenger / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000235:genetics / Q000378:metabolism*; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation
D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D004815:Epidermal Growth Factor; D006632:Histamine; D066246:ErbB Receptors