Search

Conclusions: The presented analysis of nasal polyposis using connectivity based on the PubGene literature co-citation network demonstrates that this tool can be used to identify key genes in DNA microarray studies of human polygenic diseases., Objectives: DNA microarray studies of complex diseases may reveal differential expression of hundreds of genes. According to network theory and studies of yeast cells, genes that are connected with several other genes appear to have key regulatory roles. This study aimed to examine if this principle can be translated to DNA microarray studies of human disease, using nasal polyposis as a base for the analysis., Materials and Methods: The connectivity of differentially expressed genes from a previously described microarray study of nasal polyposis before and after treatment with glucocorticoids was determined. This was done using the literature co-citation network PubGene., Results: In all, 166 genes were differentially expressed; 39 of these were previously defined as inflammatory and considered important for nasal polyposis. The connectivity of all differentially expressed genes was analysed using the PubGene literature co-citation network. Seventy-four of the 166 genes were connected to other genes. By contrast, the average number of connected genes among 100 sets of 166 randomly chosen genes was 31.5. A small number of the differentially expressed genes were highly connected, while most genes had few or no connections. This indicated a scale-free network. The most connected gene was interleukin-8, an inflammatory gene of known importance for nasal polyposis. Twenty-eight of the 74 connected genes were inflammatory (38%), compared with 11 of the 92 unconnected genes (12%), p < 0.0001. Since most evidence suggests that nasal polyps are inflammatory in their nature, this supports the hypothesis that connected genes have more disease relevance than unconnected genes.

5-HT1B receptors were discovered in human nasal mucosa using immunocytochemistry. Strong immunoreaction was seen around small blood vessels mainly confined to the smooth muscle cell layer. In contrast, no immunoreaction for 5-HT1D was seen. The possibility of local release in connection with specific target receptors suggests a role for 5-HT in the regulation of vascular tone, glandular secretion and epithelial functions and that 5-HT1B receptor agonists may be of clinical importance.

Allergic rhinitis is an inflammatory disease associated with local leukotriene release during periods of symptoms. Zileuton, a leukotriene synthesis inhibitor, is known to inhibit the release of leukotriene B4. Because we previously showed that leukotriene B4 is a potent mediator of neutrophil-dependent nasal secretion, we investigated whether Zileuton inhibited allergen-induced nasal secretion. Using a newly developed method for isolating and superfusing a nasal segment, we examined the effect of Zileuton on nasal secretion and neutrophil recruitment in ragweed-sensitized dogs. Instillation of ragweed into the nasal segment caused time-dependent increases in the volume of airway fluid and the recruitment of neutrophils. Zileuton prevented ragweed-induced neutrophil recruitment and nasal secretion. These results indicate that leukotrienes are important mediators of allergy-induced nasal secretion in dogs. Future clinical studies in allergic patients will determine whether there is a therapeutic role for leukotriene synthesis inhibitors in modulating neutrophil recruitment and hypersecretion in the nose.

mRNA encoding histamine H1 and H2 receptors were detected in the human nasal mucosa using reverse transcriptase-polymerase chain reaction. The possibility of local release in connection with specific target receptors suggests a role for histamine in the regulation of vascular tone, glandular secretion and epithelial functions.

Several studies have suggested an important role for the endothelin (ET) family of peptides in the vascular regulation of the nose. In addition, there is increasing evidence that ETs play a role in allergic airway inflammation. Endothelin is produced locally in the nose and mediates its effects via two distinct receptor subtypes, termed ET(A) and ET(B). Using reverse transcriptase-polymerase chain reaction, mRNAs encoding ET(A)- and ET(B)-receptors were detected in the human lower turbinate and sinus mucosa. The possibility of local release of ETs in connection with specific target receptors suggests a role for endothelin in the regulation of vascular tone, glandular secretion and epithelial functions.

Patients with birch pollen allergic rhinitis were treated locally, out of season, in the nasal cavity with capsaicin (30 microM) or saline. The capsaicin treatment resulted in a statistically significant reduction of symptoms upon allergen challenge, which lasted for 2 months. Saline had no effect on the symptom score upon allergen challenge. Neither capsaicin nor saline treatment had any effect on allergen challenge-induced nasal mucosal swelling monitored by acoustic rhinometry. Allergen challenge-induced eosinophil migration to the nasal mucosa was affected by neither capsaicin nor the saline treatment. The finding that capsaicin treatment reduces allergic symptoms indicates that selective, non-peptide neurokinin receptor antagonists may be an alternative in the future in the treatment of nasal allergy. However, owing to the pain involved in local capsaicin treatment this treatment is unlikely to be of clinical use.