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

Abstract

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 utilized. Intranasal challenge was performed one 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× per week and sacrificed at the end of 7 days (n=8) and 21 days (n=8). The snouts were processed for quantitative RT-PCR and compared to untreated controls for 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 mice were prepared for sinonasal histopathology. Control mice were treated with the same protocol, with intraperitoneal PBS and intranasal PBS substituted for A. fumigatis extract. Untreated mice were used for additional comparison. Results Compared to both the PBS and untreated control groups, statistically significant (p<0.05) up-regulation of MMP8 was observed in the 6 hour time point. Significant down-regulation of MMP8 was observed at 1 week. Significant up-regulation of FGF3 was observed at one week (p<0.05. BMP3 and BMP5 were significantly down-regulated 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.

Selected Bone Morphogenetic Proteins—The Possibility of Their Use in the Diagnostics and Therapy of Severe Asthma

“…In the same test, the expression of a range of cytokines from Fibroblast Growth Factors (FGF) and Matrix Metalloproteinases (MMP) was found to be elevated after exposure to a specific allergen. These findings suggest that signal transduction in cells intended for initiating the process of fibrogenesis and remodelling is initiated earlier in inflammatory illnesses [29].…”

Tissue remodeling gene expression in a murine model of chronic rhinosinusitis

“…Quantitation of the amount of target in samples is done by measuring C t and using the standard curve to determine starting copy number. Calculation of C t s, preparation of a standard curve, determination of the starting copy number, and calculation of statistical significance was performed using the ΔΔC t method with the aid of the SABiosciences PCR Array Data Analysis Web Portal 22. 18S RNA was used as the comparator.…”

“…A better understanding of the cellular and molecular processes leading to osteogenesis, fibrosis, and angiogenesis in CRS is needed in order to develop novel therapies aimed at halting or reversing CRS‐associated tissue remodeling. We have previously demonstrated acute changes in several members of the BMP, FGF, and MMP families in a mouse model of acute allergic rhinitis 22. The purpose of this study is to characterize the changes in BMP, FGF, and MMP family expression in a mouse model of CRS.…”

Inner Ear Tissue Remodeling and Ion Homeostasis Gene Alteration in Murine Chronic Otitis Media

“…As with the ion channel genes, the general pattern of remodeling gene expression was similar in the middle ear and inner ear. Previous work has shown that these genes are indeed affected by allergic fungal rhinosinusitis and otitis media in the mouse model 3, 40 . Altered expression of these genes in the inner ear in the chronic OM model has not previously been shown.…”