University of Colorado, Department of Otolaryngology, Aurora, 80045, USA.
Ann Allergy Asthma Immunol. 2011 Oct;107(4):353-9. doi: 10.1016/j.anai.2011.07.016. Epub 2011 Aug 27.
Matrix metalloproteinases (MMPs) are key enzymes responsible for extracellular matrix degradation contributing to the progressive histological changes seen in lower airway disease, including asthma. MMP-9 and TIMP-1 have also shown some role in the pathogenesis of chronic rhinosinusitis (CRS) and nasal polyposis (NP).
We aim to determine variability in expression of MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in sinus tissue from distinct patient populations presenting with nasal polyposis.
The expression of MMP-9 and TIMP-1 was investigated in nasal polyp tissue from 6 aspirin-sensitive (AS) and 6 aspirin-tolerant (AT) patients undergoing endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis (CRSwNP). Sinus mucosa from 6 patients with chronic rhinosinusitis without nasal polyposis (CRSsNP) was used as control. The MMP-9 and TIMP-1 expression was measured using immunofluorescence technique and graded using manual and computerized methods.
Expression of TIMP-1 was significantly reduced in the AS group when compared with both the AT and CRSsNP (control) groups (P < .001). The MMP-9/TIMP-1 ratio was significantly increased in the AS group when compared with other patient groups (P < .001). The MMP- 9 expression was similar between study and control groups.
These results support the importance of MMP-9 and TIMP-1 expression in nasal polyp formation. The decreased expression of TIMP-1 in AS patients may promote the effects of MMP-9 expression and thus contribute to tissue remodeling and inflammatory changes. This finding may lead to further understanding of disease severity and resistance to treatment in this group of patients, as well as the pathogenesis of nasal polyps.
基质金属蛋白酶(MMPs)是负责细胞外基质降解的关键酶,有助于下呼吸道疾病的进行性组织学变化,包括哮喘。MMP-9 和 TIMP-1 也在慢性鼻-鼻窦炎(CRS)和鼻息肉(NP)的发病机制中发挥了一定作用。
我们旨在确定在表现出鼻息肉的不同患者人群的鼻窦组织中,MMP-9 及其抑制剂组织金属蛋白酶抑制剂-1(TIMP-1)的表达是否存在差异。
使用免疫荧光技术检测 6 例阿司匹林敏感(AS)和 6 例阿司匹林耐受(AT)的慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)患者行内镜鼻窦手术时的鼻息肉组织中 MMP-9 和 TIMP-1 的表达,并使用手动和计算机化方法进行分级。使用 6 例无鼻息肉的慢性鼻-鼻窦炎(CRSsNP)患者的鼻窦黏膜作为对照。
与 AT 组和 CRSsNP(对照组)相比,AS 组的 TIMP-1 表达显著降低(P<0.001)。与其他患者组相比,AS 组的 MMP-9/TIMP-1 比值显著升高(P<0.001)。研究组和对照组的 MMP-9 表达相似。
这些结果支持 MMP-9 和 TIMP-1 表达在鼻息肉形成中的重要性。AS 患者 TIMP-1 表达降低可能促进 MMP-9 表达的作用,从而促进组织重塑和炎症变化。这一发现可能有助于进一步了解该组患者疾病的严重程度和治疗抵抗性,以及鼻息肉的发病机制。