Gene expression for NGF and NGF-receptors in the nasal mucosa of allergic rhinitic and control subjects

Abstract

Rationale We were interested in the role of nerve growth factor (NGF) in augmented nasal reactivity to sensory irritants in seasonal allergic rhinitics (SAR). Previous investigators reported that SAR subjects had elevated NGF protein in nasal lavage fluid, but had lower mRNA levels in nasal scrapings, than non-rhinitic (NR) subjects. We compared the relative expression of genes coding for NGF, high-affinity receptor (TrkA/NTRK1) and low affinity receptor (p75/TNFRS16) in the nasal mucosa of SAR and NR subjects. Methods Total RNA was extracted from nasal scrapings from 15 non-asthmatic subjects, including 6 SAR and 9 NR controls. Sampling occurred outside of aeroallergen season. cDNA was synthesized from total RNA and used as templates for quantitative real-time PCR with TaqMan probes for NGF, TrkA/NTRK1, p75/TNFRS16 and GAPDH. Relative expression of NGF and NGF receptor genes was normalized to the expression of GAPDH and expressed in delta[CT] units. Results mRNA for NGF was of low abundance and detected in only 3/6 SARs and 6/9 NRs. Compared to NGF, there was a 5-fold higher relative expression of TrkA/NTRK1 and almost 300-fold higher expression of p75/TNFRS16. NR subjects had more NGF mRNA ( p<0.10) and significantly more mRNA for p75/TNFRS16 than SAR subjects ( p<0.05). mRNA for TrkA/NTRK1 did not differ significantly between sub-groups (p=0.57). Conclusions We observed decreased transcriptional message for both NGF and low affinity NGF receptor in superficial nasal scrapings of SAR vs NR subjects. This could reflect downregulation of NGF and p75/TNFRS16 in the superficial epithelium secondary to enhanced NGF production in the glandular compartment.