Secretory Control and Intracellular Signal Transduction of Pancreatic Acinar Myofibroblast in Human

明胶酶谱检测证实人胰腺腺泡周成纤维细胞(HPFC)分泌基质金属蛋白酶(MMPs，MMPs)。在没有刺激剂的情况下，持续观察到少量MMPs的分泌，而在IL-1、β和肿瘤坏死因子-α等促炎细胞因子的存在下，MMPs的分泌明显增强。丝裂原活化蛋白激酶抑制剂芹菜素和β抑制剂PD98059均能剂量依赖性地抑制IL-1MAPK和肿瘤坏死因子-α诱导的细胞分泌增加，而p38MAPK抑制剂SB203580和p38MAPK抑制剂对其无明显影响。NF-κB的抑制剂(PTDC、TPCK)对促炎细胞因子诱导的MMP1mRNA表达无明显影响，提示PDTC和TPCK不是可阻性转录因子。综上所述，促炎性细胞因子通过一些涉及MEK相关信号通路的调节机制刺激hPFC产生MMPs。

We confirmed that matrix metalloproteinases(MMPs, MMP-1, 2, 9) were secreted from human pancreatic periacinar fibroblast-like cells(hPFCs) by gelatin gel zymography. A little amount of MMPs secretion were continuously observed in the absent of stimulants and that was remarkably enhanced in the presence of pro-inflammatory cytokines like IL-1β and TNF-α. Enhanced secretion induced by an application of IL-1β and TNF-α were reduced by an application of apigenin, a MAPK inhibitor and PD98059, a MEK inhibitor in a dose dependent manner, but not PKC inhihitor and SB203580, a p38 MAPK inhibitor.It was demonstrated that PKC-independent and MEK dependent signaling pathways induced by pro-inflammatory cytokines were closely concerned with MMP-producing system by a northern blot analysis. The inhibitors of NF-κB(PTDC, TPCK) had no effect on MMP-1 mRNA expression induced by an application of pro-inflammatory cytokines, therefore it was suggested that PDTC and TPCK not blockable transcriptional factors could be worked. Taken together, it resulted that pro-inflammatory cytokines stimulated MMPs production from hPFCs via some regulatory mechanisms involving MEK related signaling path ways.