Changes in urinary bladder cytokine mRNA and protein after cyclophosphamide-induced cystitis
Changes in urinary bladder cytokine mRNA and protein after cyclophosphamide-induced cystitis
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DOI：
10.1152/physiolgenomics.00117.2001
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发表时间：
2002-04-10
影响因子：
4.6
通讯作者：
Vizzard, MA
中科院分区：
文献类型：
--
作者：
Malley, SE;Vizzard, MA
环磷酰胺诱发的膀胱炎可改变排尿功能并引起排尿反射的重组。这种重组可能涉及膀胱中的细胞因子表达。这些研究已经确定了膀胱中可能有助于重组过程的候选细胞因子。使用RNA酶保护试验测量急性（4 h）、中间（48 h）或慢性（10天）膀胱炎后大鼠膀胱细胞因子mRNA [干扰素-γ（IFN）-γ、白细胞介素-1 α/β（IL-1 α/β）、IL-2、IL-3、IL-4、IL-5、IL-6、IL-10和肿瘤坏死因子-α/β（TNF-α/β）]的变化。免疫分析法检测膀胱细胞因子mRNA和蛋白表达的相关性。虽然在膀胱炎后的每个时间点观察到膀胱细胞因子mRNA的显著变化，但幅度不同（急性>中度>慢性）。急性膀胱炎表现出细胞因子mRNA表达的最强变化（P小于或等于0.005; IL-1 β，增加330倍; IL-2，增加20倍; IL-4，增加8倍; IL-6，增加80倍），TNF-α或TNF-β mRNA仅在急性膀胱炎后增加（2-10倍）。在48小时或10天的膀胱炎后观察到细胞因子mRNA表达的更适度的增加。细胞因子蛋白的表达通常超过mRNA的表达。CYP诱导的膀胱炎后细胞因子表达增加，单独或与其他炎症介质或生长因子联合，可能导致膀胱炎后下尿路功能改变。
Cyclophosphamide (CYP)-induced cystitis alters micturition function and produces reorganization of the micturition reflex. This reorganization may involve cytokine expression in the urinary bladder. These studies have determined candidate cytokines in the bladder that may contribute to the reorganization process. An RNase protection assay was used to measure changes in rat bladder cytokine mRNA [interferon-gamma (IFN)-gamma, interleukin-1alpha/beta (IL-1alpha/beta), IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, and tumor necrosis factor-alpha/beta (TNF-alpha/beta)] after acute (4 h), intermediate (48 h), or chronic (10 day) cystitis. The correlation between bladder cytokine mRNA and protein expression was also determined by immunoassay. Although at each time point after cystitis significant changes in bladder cytokine mRNA were observed, the magnitude differed (acute > intermediate > chronic). Acute cystitis demonstrated the most robust changes (P less than or equal to 0.005; IL-1beta, 330-fold increase; IL-2, 20-fold increase; IL-4, 8-fold increase; IL-6, 80-fold increase) in cytokine mRNA expression and TNF-alpha or TNF-beta mRNA were only increased (2-10-fold) after acute cystitis. More modest increases in cytokine mRNA expression were observed after 48-h or 10-day cystitis. Cytokine protein expression generally paralleled that of mRNA. Increased cytokine expression after CYP-induced cystitis, alone or in combination with other inflammatory mediators or growth factors, may contribute to altered lower urinary tract function after cystitis.