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Expression and Roles of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 in Allergic Nasal Mucosa.

Mori S, Pawankar R, Ozu C, Nonaka M, Yagi T, Okubo K - Allergy Asthma Immunol Res (2012)

Bottom Line: At 6 hours post-NAC, the numbers of MMP+ and TIMP+ cells did not differ significantly between HDM-exposed mucosa and control mucosa, but the ratios of MMP+ cells to TIMP+ cells were higher in HDM-exposed mucosa.At 12 hours post-NAC, the number of MMP-13+ cells tended to be higher in HDM-exposed mucosa and was strongly correlated with the number of eosinophils.Quantitatively, the levels of MMP-2 and MMP-13 were significantly higher than the MMP-9 level, and the TIMP-2 level was significantly higher than the TIMP-1 level in allergic nasal mucosa.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan.

ABSTRACT

Purpose: Allergic rhinitis (AR) and asthma share many characteristics, but structural changes are observed far less often in AR. Matrix metalloproteinases (MMPs) constitute a family of Zn-dependent endopeptidases that can decompose the extracellular matrix and basement membrane, and regulate cell infiltration. We analyzed the expression of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in allergic nasal mucosa after nasal allergen challenge (NAC) and determined their relationship to inflammatory cells.

Methods: Nasal mucosa specimens were obtained at surgery performed for hypertrophied turbinates. We performed NAC with house dust mite (HDM) allergen disks and control disks, and took biopsies at 30 minutes, 6 hours, and 12 hours after NAC. Cells expressing MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2, as well as eosinophils and mast cells, were analyzed immunohistochemically. The MMPs and TIMPs in allergic nasal mucosa were quantified using enzyme-linked immunosorbent assays.

Results: At 30 minutes post-NAC, HDM-exposed nasal mucosa exhibited significantly more MMP-2+, MMP-9+, MMP-13+, TIMP-1+, and TIMP-2+ cells compared with control mucosa, and the numbers of MMP-9+ and TIMP-1+ cells correlated strongly with the number of mast cells. At 6 hours post-NAC, the numbers of MMP+ and TIMP+ cells did not differ significantly between HDM-exposed mucosa and control mucosa, but the ratios of MMP+ cells to TIMP+ cells were higher in HDM-exposed mucosa. At 12 hours post-NAC, the number of MMP-13+ cells tended to be higher in HDM-exposed mucosa and was strongly correlated with the number of eosinophils. Quantitatively, the levels of MMP-2 and MMP-13 were significantly higher than the MMP-9 level, and the TIMP-2 level was significantly higher than the TIMP-1 level in allergic nasal mucosa.

Conclusions: We demonstrated increased expression of MMP-2, MMP-9, and MMP-13 in allergic nasal mucosa, high MMPs-to-TIMP-1 ratios, and a strong correlation between MMP-9 and mast cells and between MMP-13 and eosinophils. The imbalance between MMPs and TIMPs may contribute to the migration of inflammatory cells such as eosinophils and mast cells to the nasal mucosa of AR patients, suggesting a possible active role of MMPs in AR.

No MeSH data available.


Related in: MedlinePlus

Correlation of MMP-9+ and TIMP-1+ cells with mast cells in the nasal mucosa of PAR patients. (A) There was a strong correlation between the number of mast cells and the number of MMP-9+ cells at 30 min after NAC with HDM allergen disks. (r=0.8, P<0.02, by Spearman's rank correlation coefficient; n=10.) (B) There was a strong correlation between the number of mast cells and the number of TIMP-1+ cells at 30 min after NAC with HDM allergen disks. (r=0.8, P<0.05, by Spearman's rank correlation coefficient; n=10.)
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Figure 5: Correlation of MMP-9+ and TIMP-1+ cells with mast cells in the nasal mucosa of PAR patients. (A) There was a strong correlation between the number of mast cells and the number of MMP-9+ cells at 30 min after NAC with HDM allergen disks. (r=0.8, P<0.02, by Spearman's rank correlation coefficient; n=10.) (B) There was a strong correlation between the number of mast cells and the number of TIMP-1+ cells at 30 min after NAC with HDM allergen disks. (r=0.8, P<0.05, by Spearman's rank correlation coefficient; n=10.)

Mentions: Mast cells are increased specifically in the nasal epithelium of patients with allergic rhinitis. To understand the relationship between MMPs and the migration of mast cells to the nasal mucosa, particularly intraepithelial migration of mast cells, we analyzed the correlation between the number of cells expressing MMPs and the number of cells expressing tryptase, a marker for mast cells. At 30 minutes after NAC, the number of mast cells was strongly correlated with the number of MMP-9+ cells (P<0.05, r=0.77) and the number of TIMP-1+ cells (P<0.05, r=0.78) (Fig. 5).


Expression and Roles of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 in Allergic Nasal Mucosa.

Mori S, Pawankar R, Ozu C, Nonaka M, Yagi T, Okubo K - Allergy Asthma Immunol Res (2012)

Correlation of MMP-9+ and TIMP-1+ cells with mast cells in the nasal mucosa of PAR patients. (A) There was a strong correlation between the number of mast cells and the number of MMP-9+ cells at 30 min after NAC with HDM allergen disks. (r=0.8, P<0.02, by Spearman's rank correlation coefficient; n=10.) (B) There was a strong correlation between the number of mast cells and the number of TIMP-1+ cells at 30 min after NAC with HDM allergen disks. (r=0.8, P<0.05, by Spearman's rank correlation coefficient; n=10.)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3378930&req=5

Figure 5: Correlation of MMP-9+ and TIMP-1+ cells with mast cells in the nasal mucosa of PAR patients. (A) There was a strong correlation between the number of mast cells and the number of MMP-9+ cells at 30 min after NAC with HDM allergen disks. (r=0.8, P<0.02, by Spearman's rank correlation coefficient; n=10.) (B) There was a strong correlation between the number of mast cells and the number of TIMP-1+ cells at 30 min after NAC with HDM allergen disks. (r=0.8, P<0.05, by Spearman's rank correlation coefficient; n=10.)
Mentions: Mast cells are increased specifically in the nasal epithelium of patients with allergic rhinitis. To understand the relationship between MMPs and the migration of mast cells to the nasal mucosa, particularly intraepithelial migration of mast cells, we analyzed the correlation between the number of cells expressing MMPs and the number of cells expressing tryptase, a marker for mast cells. At 30 minutes after NAC, the number of mast cells was strongly correlated with the number of MMP-9+ cells (P<0.05, r=0.77) and the number of TIMP-1+ cells (P<0.05, r=0.78) (Fig. 5).

Bottom Line: At 6 hours post-NAC, the numbers of MMP+ and TIMP+ cells did not differ significantly between HDM-exposed mucosa and control mucosa, but the ratios of MMP+ cells to TIMP+ cells were higher in HDM-exposed mucosa.At 12 hours post-NAC, the number of MMP-13+ cells tended to be higher in HDM-exposed mucosa and was strongly correlated with the number of eosinophils.Quantitatively, the levels of MMP-2 and MMP-13 were significantly higher than the MMP-9 level, and the TIMP-2 level was significantly higher than the TIMP-1 level in allergic nasal mucosa.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan.

ABSTRACT

Purpose: Allergic rhinitis (AR) and asthma share many characteristics, but structural changes are observed far less often in AR. Matrix metalloproteinases (MMPs) constitute a family of Zn-dependent endopeptidases that can decompose the extracellular matrix and basement membrane, and regulate cell infiltration. We analyzed the expression of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in allergic nasal mucosa after nasal allergen challenge (NAC) and determined their relationship to inflammatory cells.

Methods: Nasal mucosa specimens were obtained at surgery performed for hypertrophied turbinates. We performed NAC with house dust mite (HDM) allergen disks and control disks, and took biopsies at 30 minutes, 6 hours, and 12 hours after NAC. Cells expressing MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2, as well as eosinophils and mast cells, were analyzed immunohistochemically. The MMPs and TIMPs in allergic nasal mucosa were quantified using enzyme-linked immunosorbent assays.

Results: At 30 minutes post-NAC, HDM-exposed nasal mucosa exhibited significantly more MMP-2+, MMP-9+, MMP-13+, TIMP-1+, and TIMP-2+ cells compared with control mucosa, and the numbers of MMP-9+ and TIMP-1+ cells correlated strongly with the number of mast cells. At 6 hours post-NAC, the numbers of MMP+ and TIMP+ cells did not differ significantly between HDM-exposed mucosa and control mucosa, but the ratios of MMP+ cells to TIMP+ cells were higher in HDM-exposed mucosa. At 12 hours post-NAC, the number of MMP-13+ cells tended to be higher in HDM-exposed mucosa and was strongly correlated with the number of eosinophils. Quantitatively, the levels of MMP-2 and MMP-13 were significantly higher than the MMP-9 level, and the TIMP-2 level was significantly higher than the TIMP-1 level in allergic nasal mucosa.

Conclusions: We demonstrated increased expression of MMP-2, MMP-9, and MMP-13 in allergic nasal mucosa, high MMPs-to-TIMP-1 ratios, and a strong correlation between MMP-9 and mast cells and between MMP-13 and eosinophils. The imbalance between MMPs and TIMPs may contribute to the migration of inflammatory cells such as eosinophils and mast cells to the nasal mucosa of AR patients, suggesting a possible active role of MMPs in AR.

No MeSH data available.


Related in: MedlinePlus