Role of the transient receptor potential vanilloid type 1 channel in renal inflammation induced by lipopolysaccharide in mice.
Role of the transient receptor potential vanilloid type 1 channel in renal inflammation induced by lipopolysaccharide in mice.
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DOI：
10.1152/ajpregu.00163.2012
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Youping Wang;Donna H. Wang
中科院分区：
文献类型：
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作者：
Youping Wang;Donna H. Wang
为了确定瞬时受体电位香草酸1型（TRPV 1）通道在肾脏炎症调节中的作用，将脂多糖（LPS，3 mg/kg）腹腔注射到野生型（WT）和TRPV 1无效突变型（TRPV 1（-/-））小鼠中。分别于注射LPS后6 h和24 h收集大鼠肾脏和血清，进行形态学分析和促炎细胞因子测定。通过遥测系统测定，LPS注射导致WT和TRPV 1（-/-）小鼠出现相似程度的一过性低血压和心动过缓。与WT小鼠相比，LPS给药引起TRPV 1（-/-）小鼠实质红细胞充血和完整肾小球结构消退。TRPV 1（-/-）小鼠注射LPS后24小时血清肌酐水平高于WT小鼠。TRPV 1（-/-）小鼠在LPS注射后6 h和24 h肾脏中的神经细胞和巨噬细胞浸润均大于WT小鼠。与WT小鼠相比，TRPV 1（-/-）小鼠在LPS注射后6 h的血清细胞因子水平，包括肿瘤坏死因子（TNF）-α、IL-1β和IL-6均较高。同样，TRPV 1（-/-）小鼠在LPS注射后6 h，肾趋化因子水平（包括角质细胞衍生趋化因子和巨噬细胞炎性蛋白）高于WT小鼠。TRPV 1（-/-）小鼠注射LPS后6 h和24 h肾组织VCAM-1和ICAM-1的表达较WT小鼠进一步升高。与WT小鼠相比，TRPV 1（-/-）小鼠在LPS注射后6 h肾核因子-κB（NF-κB）活性进一步升高。WT小鼠中的药理学阻断TRPV 1显示与TRPV 1（-/-）小鼠相似的肾和血清炎症反应加重。因此，TRPV 1基因消融加剧了LPS诱导的肾组织和功能损伤，包括肾中性粒细胞和巨噬细胞浸润加重，趋化因子和粘附分子水平升高，肾小球细胞增生伴随血清肌酐和细胞因子水平进一步升高。这些结果表明，TRPV 1在LPS攻击过程中被激活，这可能是通过减少肾脏炎症反应而对LPS诱导的肾损伤的保护机制。
To determine the role of the transient receptor potential vanilloid type 1 (TRPV1) channel in the regulation of renal inflammation, lipopolysaccharide (LPS, 3 mg/kg) was intraperitoneally injected into wild-type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice. The kidney and serum were collected 6 or 24 h after LPS injection for morphological analysis and proinflammatory cytokine assay. LPS injection led to a similar degree of transient hypotension and bradycardia in WT and TRPV1(-/-) mice determined by a telemetry system. LPS administration caused parenchymal red blood cell congestion and fading of intact glomerular structure in TRPV1(-/-) compared with WT mice. Serum creatinine levels were higher 24 h after LPS injection in TRPV1(-/-) than in WT mice. Neutrophil and macrophage infiltration in the kidneys was greater 6 h for the former and 24 h for both after LPS injection in TRPV1(-/-) than in WT mice. Serum cytokine levels including tumor necrosis factor (TNF)-α, IL-1β, and IL-6 were higher 6 h after LPS injection in TRPV1(-/-) compared with WT mice. Likewise, renal chemokine levels including keratinocyte-derived chemokines and macrophage inflammatory protein were higher 6 h after LPS injection in TRPV1(-/-) than in WT mice. Renal VCAM-1 and ICAM-1 expression was further elevated 6 h for the former and 24 h for the latter after LPS injection in TRPV1(-/-) than in WT mice. Renal nuclear factor-κB (NF-κB) activity was further increased 6 h after LPS injection in TRPV1(-/-) compared with WT mice. Pharmacological blockade TRPV1 in WT mice showed aggravated renal and serum inflammatory responses resembling that of TRPV1(-/-) mice. Thus TRPV1 gene ablation exacerbates LPS-induced renal tissue and function injury, including aggravated renal neutrophil and macrophage infiltration, chemokine and adhesion molecule levels, and glomerular hypercellularity accompanying with further increased serum creatinine and cytokine levels. These results indicate that TRPV1 is activated during LPS challenge, which may constitute a protect mechanism against LPS-induced renal injury via reducing renal inflammatory responses.