From the State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing People's Republic of China.
J Trauma Acute Care Surg. 2014 Mar;76(3):762-70. doi: 10.1097/TA.0b013e3182ab0723.
Studies have shown that interleukin 1β (IL-1β) participates in the down-regulation of vascular reactivity via both nitric oxide-dependent and nitric oxide-independent mechanisms during shock. However, the precise mechanisms of nitric oxide-independent pathway remain to be established.
The effect of IL-1β on the expression of α1 adrenergic receptors (α1AR) and the relationship with Janus kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway were observed using a rabbit model of lipopolysaccharide (LPS)-induced endotoxemia and superior mesenteric arteries (SMAs) in vivo and in vitro, respectively.
The vascular reactivity of SMAs to α1AR agonist (phenylephrine) displayed a biphasic change after LPS (significantly increased at 0.5 hour following LPS and then markedly decreased after 2 hours), the α1A, α1B and α1DAR messenger RNA (mRNA) and protein expression seemed a time-dependent decrease following LPS administration, α1A and α1DAR decreased more obviously than α1BAR. IL-1ra (4 µg/mL) partly reversed LPS-induced the decrease of vascular reactivity and down-regulation of α1AR expression. In vitro incubation with IL-1β (12.5-50 ng/mL) significantly decreased the vascular reactivity of SMA to phenylephrine and the expression of α1AR mRNA and protein and elevated the DNA binding ability of STAT3. AG490 (10 µmol/L), an inhibitor of JAK2, partly reversed the IL-1β-induced down-regulation of vascular reactivity and α1AR mRNA and protein expression and suppressed the DNA binding ability of STAT3.
IL-1β participates in the regulation of vascular hyporeactivity following endotoxemia in rabbit. The mechanism is related to the down-regulation of α1AR expression through activating the JAK2-STAT3 pathway.
研究表明，白细胞介素 1β（IL-1β）通过一氧化氮（NO）依赖和非依赖机制参与休克时血管反应性的下调。然而，NO 非依赖途径的确切机制仍有待确定。
分别采用兔内毒素血症模型和体内、体外肠系膜上动脉（SMA）观察 IL-1β对α1肾上腺素能受体（α1AR）表达的影响及其与 Janus 激酶 2-信号转导和转录激活因子 3（JAK2-STAT3）通路的关系。
SMA 对α1AR 激动剂（苯肾上腺素）的血管反应性呈双相变化，LPS 后（LPS 后 0.5 小时明显增加，2 小时后明显下降），α1A、α1B 和 α1DAR 信使 RNA（mRNA）和蛋白表达似乎呈时间依赖性下降，α1A 和α1DAR 下降较α1BAR 更为明显。IL-1ra（4μg/mL）部分逆转 LPS 诱导的血管反应性降低和α1AR 表达下调。体外孵育 IL-1β（12.5-50ng/mL）显著降低 SMA 对苯肾上腺素的血管反应性和α1AR mRNA 和蛋白的表达，并增加 STAT3 的 DNA 结合能力。JAK2 抑制剂 AG490（10μmol/L）部分逆转了 IL-1β 诱导的血管反应性和α1AR mRNA 和蛋白表达下调，并抑制了 STAT3 的 DNA 结合能力。
IL-1β参与了兔内毒素血症后血管低反应性的调节。其机制与通过激活 JAK2-STAT3 通路下调α1AR 表达有关。
