Wang Xin, Zhao Chunyuan, Ji Wenjun, Xu Yuan, Guo Huamin
Department of Otorhinolaryngology & Head and Neck Surgery, Second Hospital Affiliated to Harbin Medical University Harbin, China.
Department of ENT, People Hospital of Hailin City Hailin, China.
Int J Clin Exp Pathol. 2015 Feb 1;8(2):1199-212. eCollection 2015.
In order to explore the role of innate immunity in the remodeling of CRS (chronic rhinosinusitis), we investigated the correlation between TLR2, TLR4 and remodeling involved cytokines and histopathological features. Immunohistochemical staining was applied to detect the expression of TLR2, TLR4 and TGF-β1. Masson staining was used for observing the collagen deposition. The other histopathologic features of remodeling were observed by hemotoxylin and eosin (HE) staining. Nasal epithelial cell culture was used to elucidate the effect of TLR2, TLR4 agonists and inhibitors on the expression of TGF-β1 and MMP-9. The association study showed that the significantly higher expression of TLR2, TLR4, TGF-β1 and collagen appeared in CRSsNP (chronic rhinosinusitis without nasal polyps) patients compared with CRSwNP (chronic rhinosinusitis with nasal polyps) patients. In CRSsNP, patients with a severe epithelial damage (score 3) had a significantly higher expression of TLR2 than patients with mild epithelial damage (score ≤ 2) (P < 0.05). Moreover the expression of TLR2 correlated negatively with squamous hyperplasia in CRSsNP, and positively with gland hyperplasia in CRSwNP. The expression of TLR2 and TLR4 was closely related to neutrophil infiltration in CRSsNP (P < 0.01). TGF-β1 was downregulated by TLR2 agonist in CRSwNP and upregulated by TLR4 agonist in CRSsNP (P < 0.05). MMP-9 was upregulated by TLR4 agonist in CRSwNP (P < 0.05). TLR2 and TLR4 had close relationship with TGF-β1 and the histologic features of remodeling, especially collagen deposition and neutrophil infiltration in CRSsNP. The innate immunity could influence the histologic characteristics and involved cytokines through TLR2 and TLR4 in the remodeling of CRS.
为了探讨天然免疫在慢性鼻-鼻窦炎（CRS）重塑过程中的作用，我们研究了Toll样受体2（TLR2）、Toll样受体4（TLR4）与重塑相关细胞因子及组织病理学特征之间的相关性。采用免疫组织化学染色检测TLR2、TLR4及转化生长因子-β1（TGF-β1）的表达。采用Masson染色观察胶原沉积情况。通过苏木精-伊红（HE）染色观察重塑的其他组织病理学特征。采用鼻上皮细胞培养来阐明TLR2、TLR4激动剂和抑制剂对TGF-β1和基质金属蛋白酶-9（MMP-9）表达的影响。关联研究显示，与慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）患者相比，慢性鼻-鼻窦炎不伴鼻息肉（CRSsNP）患者中TLR2、TLR4、TGF-β1及胶原的表达显著更高。在CRSsNP中，上皮损伤严重（评分为3分）的患者TLR2表达显著高于上皮损伤轻微（评分≤2分）的患者（P<0.05）。此外，在CRSsNP中，TLR2表达与鳞状上皮增生呈负相关，而在CRSwNP中与腺体增生呈正相关。在CRSsNP中，TLR2和TLR4的表达与中性粒细胞浸润密切相关（P<0.01）。在CRSwNP中，TLR2激动剂可使TGF-β1表达下调，而在CRSsNP中，TLR4激动剂可使TGF-β1表达上调（P<0.05）。在CRSwNP中，TLR4激动剂可使MMP-9表达上调（P<0.05）。TLR2和TLR4与TGF-β1及重塑的组织学特征密切相关，尤其是CRSsNP中的胶原沉积和中性粒细胞浸润。在CRS重塑过程中，天然免疫可通过TLR2和TLR4影响组织学特征及相关细胞因子。
