Bach2在嗜酸粒细胞性慢性鼻-鼻窦炎伴鼻息肉组织中表达及临床意义
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摘要
目的 探究BTB与CNC同源基因2(Bach2)在不同类型慢性鼻-鼻窦炎(CRS)中的表达及临床意义。方法 43例慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)患者中,嗜酸粒细胞性慢性鼻-鼻窦炎伴鼻息肉(ECRS)19例,非嗜酸粒细胞性慢性鼻-鼻窦炎伴鼻息肉(non-ECRS)24例,另有20例对照受试者,分别收集鼻息肉和筛窦黏膜。通过定量逆转录-聚合酶链反应、免疫组织化学染色和蛋白质印迹法测定收集的组织样品中Bach2的表达情况;通过苏木精-伊红染色,测定组织中嗜酸粒细胞数。疾病的严重程度通过计算机断层扫描(CT)、鼻内窥镜检查和受试者症状来评估。结果 Bach2主要表达在鼻上皮细胞层中。Bach2的mRNA和蛋白表达在ECRS中显著低于non-ECRS,但高于对照组(P<0.05,P<0.01)。Bach2的mRNA表达水平与所有ECRS患者的CT扫描结果、鼻内镜评分及组织中每高倍镜视野中的嗜酸粒细胞数之间呈一定的相关性(P<0.01,P<0.05,P<0.01),而与VAS评分间无明显相关性(P>0.05)。结论 Bach2在ECRS中表达与non-ECRS相比较低,致ECRS中嗜酸性炎症,并且与其疾病严重程度有关。
Objective To explore the expression and clinical significance of BTB and CNC homology 2(Bach2) in different types of chronic rhinosinusitis(CRS). Methods In this study, nasal polyps and ethmoid sinus mucosa were enrolled from 43 CRS with nasal polyps(CRSwNP) patients [eosinophil CRSwNP(ECRS):n=19; non-ECRS:n=24] and 20 control subjects,respectively. The expression of Bach2 in sinonasal mucosal samples was detected by quantitative reverse transcript–polymerse chain reaction, immunohistochemistry and Western blot, and the number of eosinophils insinonasal mucosal samples was assessed byhematoxylin-eosin staining. The severity of disease was scored by computed tomography(CT) scan, nasal endoscopy scan, and symptoms. Results The Bach2 was mainly located in the nasal mucosa epithelium. The mRNA and protein expression of Bach2 was significantly lower in ECRS than in non-ECRS, but higher than in control(P<0.05, P<0.01). There was a correlation between the mRNA expression level of Bach2 and the CT scan results, nasal endoscopy scores, and eosinophil counts per high power field in all ECRS patients(P<0.01, P<0.05, P<0.01), but there was not significant correlation with the VAS score(P>0.05). Conclusion Bach2 is lower expressed in ECRS patients compared with non-ECRS, it contributes to eosinophilic inflammation in ECRS, and is related to the disease severity.
Objective To explore the expression and clinical significance of BTB and CNC homology 2(Bach2) in different types of chronic rhinosinusitis(CRS). Methods In this study, nasal polyps and ethmoid sinus mucosa were enrolled from 43 CRS with nasal polyps(CRSwNP) patients [eosinophil CRSwNP(ECRS):n=19; non-ECRS:n=24] and 20 control subjects,respectively. The expression of Bach2 in sinonasal mucosal samples was detected by quantitative reverse transcript–polymerse chain reaction, immunohistochemistry and Western blot, and the number of eosinophils insinonasal mucosal samples was assessed byhematoxylin-eosin staining. The severity of disease was scored by computed tomography(CT) scan, nasal endoscopy scan, and symptoms. Results The Bach2 was mainly located in the nasal mucosa epithelium. The mRNA and protein expression of Bach2 was significantly lower in ECRS than in non-ECRS, but higher than in control(P<0.05, P<0.01). There was a correlation between the mRNA expression level of Bach2 and the CT scan results, nasal endoscopy scores, and eosinophil counts per high power field in all ECRS patients(P<0.01, P<0.05, P<0.01), but there was not significant correlation with the VAS score(P>0.05). Conclusion Bach2 is lower expressed in ECRS patients compared with non-ECRS, it contributes to eosinophilic inflammation in ECRS, and is related to the disease severity.
引文
[1] 中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组.慢性鼻-鼻窦炎诊断和治疗指南(2012年,昆明)[J].中华耳鼻咽喉头颈外科杂志,2013,48(2):92-4.
[2] Hsu J,Peters A T.Pathophysiology of chronic rhinosinusitis with nasal polyp[J].Am J Rhinol Allergy,2011,25(5):285-90.
[3] Chin D,Harvey R J.Nasal polyposis:an inflammatory condition requiring effective anti-inflammatory treatment[J].Curr Opin Otolaryngol Head Neck Surg,2013,21(1):23-30.
[4] Soler Z M,Sauer D,Mace J,et al.Impact of mucosal eosinophilia and nasal polyposis on quality-of-life outcomes after sinus surgery[J].Otolaryngol Head Neck Surg,2010,142(1):64-71.
[5] Kjeldsen M K,Dybkaer K,Liu J,et al.BACH2 (BTB and CNC homology 1,basic leucine zipper transcription factor 2)[J].Atlas Genet Cytogenet Oncol Haematol,2010,14(10):930-3.
[6] Kim E H,Gasper D J,Lee S H,et al.Bach2 regulates homeostasis of Foxp3+ regulatory T cells and protects against fatal lung disease in mice[J].J Immunol,2014,192(3):985-95.
[7] Roychoudhuri R,Hirahara K,Mousavi K,et al.BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis[J].Nature,2013,498(7455):506-10.
[8] Cao P P,Li H B,Wang B F,et al.Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese[J].J Allergy Clin Immunol,2009,124(3):478-84.e2.
[9] Tsukumo S,Unno M,Muto A,et al.Bach2 maintains T cells in a naive state by suppressing effector memory-related genes[J].Pnas,2013,110(26):10735-40.
[10] Soyka M B,Wawrzyniak P,Eiwegger T,et al.Defective epithelial barrier in chronic rhinosinusitis:the regulation of tight junctions by IFN-γ and IL-4[J].J Allergy Clin Immunol,2012,130(5):1087-96.e10.
[11] Richer S,Truong-Tran A D,Carter R,et al.Epithelial genes in chronic rhinosinusitis with and without nasal polyps[J].Am J Rhinol,2008,22(3):228-34.
[12] Kuwahara M,Ise W,Ochi M,et al.Bach2-Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop[J].Nat Commun,2016,7:12596.
[13] Pitrez P M C,Brennan S,Turner S,et al.Nasal wash as an alternative to bronchoalveolar lavage in detecting early pulmonary inflammation in children with cystic fibrosis[J].Respirology,2005,10(2):177-82.
[14] Yamashita M,Kuwahara M.The critical role of Bach2 in regulating type-2 chronic airway inflammation[J].Int Immunol,2018,30(9):397-402.
[2] Hsu J,Peters A T.Pathophysiology of chronic rhinosinusitis with nasal polyp[J].Am J Rhinol Allergy,2011,25(5):285-90.
[3] Chin D,Harvey R J.Nasal polyposis:an inflammatory condition requiring effective anti-inflammatory treatment[J].Curr Opin Otolaryngol Head Neck Surg,2013,21(1):23-30.
[4] Soler Z M,Sauer D,Mace J,et al.Impact of mucosal eosinophilia and nasal polyposis on quality-of-life outcomes after sinus surgery[J].Otolaryngol Head Neck Surg,2010,142(1):64-71.
[5] Kjeldsen M K,Dybkaer K,Liu J,et al.BACH2 (BTB and CNC homology 1,basic leucine zipper transcription factor 2)[J].Atlas Genet Cytogenet Oncol Haematol,2010,14(10):930-3.
[6] Kim E H,Gasper D J,Lee S H,et al.Bach2 regulates homeostasis of Foxp3+ regulatory T cells and protects against fatal lung disease in mice[J].J Immunol,2014,192(3):985-95.
[7] Roychoudhuri R,Hirahara K,Mousavi K,et al.BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis[J].Nature,2013,498(7455):506-10.
[8] Cao P P,Li H B,Wang B F,et al.Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese[J].J Allergy Clin Immunol,2009,124(3):478-84.e2.
[9] Tsukumo S,Unno M,Muto A,et al.Bach2 maintains T cells in a naive state by suppressing effector memory-related genes[J].Pnas,2013,110(26):10735-40.
[10] Soyka M B,Wawrzyniak P,Eiwegger T,et al.Defective epithelial barrier in chronic rhinosinusitis:the regulation of tight junctions by IFN-γ and IL-4[J].J Allergy Clin Immunol,2012,130(5):1087-96.e10.
[11] Richer S,Truong-Tran A D,Carter R,et al.Epithelial genes in chronic rhinosinusitis with and without nasal polyps[J].Am J Rhinol,2008,22(3):228-34.
[12] Kuwahara M,Ise W,Ochi M,et al.Bach2-Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop[J].Nat Commun,2016,7:12596.
[13] Pitrez P M C,Brennan S,Turner S,et al.Nasal wash as an alternative to bronchoalveolar lavage in detecting early pulmonary inflammation in children with cystic fibrosis[J].Respirology,2005,10(2):177-82.
[14] Yamashita M,Kuwahara M.The critical role of Bach2 in regulating type-2 chronic airway inflammation[J].Int Immunol,2018,30(9):397-402.