八肽胆囊收缩素对脂多糖诱导小鼠分泌IL-12的影响及其机制研究

Effect of CCK-8 on signal mechanisms of IL-12 secretion in LPS-induced mice

目的:观察八肽胆囊收缩素(CCK-8)对脂多糖诱导小鼠分泌IL-12的影响,探讨核因子-κB(NF-κB)和p38丝裂原活化蛋白激酶(p38 MAPK)的信号转导作用。方法:雌性BALB/c小鼠经LPS诱导后分别给予CCK及CCK-A、B受体拮抗剂。ELISA法检测小鼠血清及肺、脾组织中IL-12p40、p70的表达;Western blot-ting法检测肺脏、脾脏IκB、p38 MAPK的表达;EMSA法检测肺、脾组织中NF-κB/DNA的结合活性。结果:CCK-8进一步提高了LPS诱导的小鼠血清及肺、脾组织中IL-12p40、p70的表达;抑制IκB磷酸化和NF-κB/DNA结合活性;促进p38 MAPK磷酸化。而CCK-A受体拮抗剂(CR-1409)及CCK-B受体拮抗剂(CR-2945)部分逆转了CCK-8的效应。结论:CCK-8可促进LPS诱导小鼠分泌IL-12,p38 MAPK可能参与了其信号转导机制,而NF-κB途径可能并未参与CCK-8促IL-12分泌这一过程。

AIM： To study the effects of CCK -8 on IL - 12 secretion in LPS - induced mice and to investigate the signal transduction mechanisms involving NF - κB and p38 MAPK. METHODS： Female BALB/c mice were induced by LPS in the presence or absence of CCK - 8, CCK - A or B receptor antagonist. The productions of IL - 12p40 and p70 in the sera, lung and spleen tissues were evaluated by ELISA. Changes of plκB, p - p38 protein expression and the NF - κB/DNA binding activity were examined by Western blotting and EMSA, respectively. RESULTS： CCK - 8 increased the expressions of IL- 12p40, p70 in the serum, lung and spleen tissues of LPS - induced mice, inhibited IκB phosphorylation and NF- κB/DNA binding activity, increased p38 phosphorylation. CONCLUSION： CCK -8 increases the production of IL - 12 in LPS - induced mice probably via activating p38 MAPK. NF - κB might not mediate the activating effect of CCK - 8 on IL - 12 production.