Altered expression of tissue remodeling genes in a mouse model of acute allergic rhinitis.

BACKGROUND

Osteogenesis, fibrosis, and scarring are prominent pathologic changes resulting from chronic sinonasal inflammation, and these tissue changes may increase the degree of disease symptomatology and the level of surgical difficulty. Members of the bone morphogenetic protein (BMP) and fibroblast growth factor (FGF) families of cytokines and the matrix metalloproteinase (MMP) family of endopeptidases are known to regulate tissue remodeling in other disease processes, but their role in acute and chronic sinonasal inflammation remains undefined.

METHODS

A previously described mouse model of acute allergic rhinitis secondary to Aspergillus fumigatis exposure in BALB/C mice was used. Intranasal challenge was performed 1 week following intraperitoneal sensitization with A. fumigatis extract and mice were sacrificed 6 hours (n = 8) and 24 hours (n = 8) later. Additional mice were intranasally challenged 3 times per week and sacrificed at the end of 7 days (n = 8) and 21 days (n = 8). The snouts were processed for quantitative reverse-transcription polymerase chain reaction (RT-PCR) and compared to untreated controls for messenger ribonucleic acid (mRNA) expression of BMP1, 2, 3, 4, 5, 6, 7, 8a, 8b, 9, 10, FGF1, 2, 3, 4, 5, 6, 7, 8, 10, and MMP1a, 2, 3, 7, 8, 9, 12, and 14. Additional 21-day-old mice were prepared for sinonasal histopathology. Control mice were treated with the same protocol, with intraperitoneal phosphate-buffered saline (PBS) and intranasal PBS substituted for A. fumigatis extract. Untreated mice were used for additional comparison.

RESULTS

Compared to both the PBS-treated and untreated control groups, statistically significant (p < 0.05) upregulation of MMP8 was observed in the 6-hour time point. Significant downregulation of MMP8 was observed at 1 week. Significant upregulation of FGF3 was observed at 1 week (p < 0.05). BMP3 and BMP5 were significantly downregulated in the 1-week group (p < 0.05). The mice exhibited histologic sinonasal changes consistent with allergic inflammation.

CONCLUSION

Intranasal exposure to A. fumigatis results in altered expression of several tissue remodeling cytokines at varying time points in the acute allergic rhinitis mouse model. These changes in cytokine regulation may subsequently contribute to sinonasal osteogenesis, scarring, and fibrosis as seen in chronic rhinosinusitis.