Department of Otolaryngology-Head and Neck Surgery, Xuan Wu Hospital, Capital Medical University, 100053, Beijing, People's Republic of China.
Inflamm Res. 2009 Oct;58(10):649-58. doi: 10.1007/s00011-009-0030-x. Epub 2009 Mar 25.
To investigate the signal pathways involved in cyclooxygenase-2 (COX-2) expression in chronic rhinosinusitis (CRS).
The expressions of COX-2, p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-regulated kinase (ERK), and nuclear factor kappa B (NF-kappaB) in nasal mucosa were detected by immunohistological stain and polymerase chain reaction (PCR). Their expressions and prostaglandin E2 (PGE(2)) release were determined by PCR, Western blot and enzyme immunoassay (EIA) in human nasal epithelia (HNE) cells after lipopolysaccharide (LPS) induction, and/or small interfering RNA (siRNA) transfection.
Positive protein expressions of COX-2, p38MAPK, ERK, NF-kappaB subunits were detected in epithelial and inflammatory cells. Their mRNA levels were significantly higher in CRS than controls (P < 0.05). The expressions varied in time and concentration-dependent manner in LPS-induced HNE cells. COX-2 expression was suppressed by siRNAs of P38MAPK, ERK, and NF-kappaB; however, COX-2-specific siRNA had no blocking effect on them. SiRNAs of P38MAPK or ERK could block NF-kappaB, but NF-kappaB-specific siRNA had no blocking effect on the former. SiRNA of p38MAPK, or ERK did not inhibit each other.
Upregulation of COX-2 expression suggested its role as a mediator in CRS. ERK and p38MAPK pathways were involved in signaling COX-2 through NF-kappaB pathway.
研究环氧合酶-2（COX-2）在慢性鼻-鼻窦炎（CRS）表达的信号通路。
采用免疫组织化学染色和聚合酶链反应（PCR）检测鼻黏膜中 COX-2、p38 丝裂原活化蛋白激酶（p38MAPK）、细胞外信号调节激酶（ERK）和核因子 kappa B（NF-κB）的表达。通过聚合酶链反应（PCR）、Western blot 和酶联免疫吸附试验（EIA），检测脂多糖（LPS）诱导后和/或小干扰 RNA（siRNA）转染后，人鼻上皮（HNE）细胞中 COX-2、前列腺素 E2（PGE2）的释放及其表达情况。
在上皮细胞和炎症细胞中检测到 COX-2、p38MAPK、ERK、NF-κB 亚单位的阳性蛋白表达。CRS 组的 mRNA 水平明显高于对照组（P < 0.05）。在 LPS 诱导的 HNE 细胞中，其表达呈时间和浓度依赖性变化。p38MAPK、ERK 和 NF-κB 的 siRNA 可抑制 COX-2 的表达；然而，COX-2 特异性 siRNA 对其无阻断作用。p38MAPK 或 ERK 的 siRNA 可阻断 NF-κB，但 NF-κB 特异性 siRNA 对前者无阻断作用。p38MAPK 或 ERK 的 siRNA 之间没有相互抑制作用。
COX-2 表达上调提示其在 CRS 中作为一种介质的作用。ERK 和 p38MAPK 途径通过 NF-κB 途径参与信号转导 COX-2。
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