MCP-1 but not CINC synthesis is increased in rat pancreatic acini in response to cerulein hyperstimulation
MCP-1 but not CINC synthesis is increased in rat pancreatic acini in response to cerulein hyperstimulation
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DOI：
10.1152/ajpgi.00031x.2002
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发表时间：
2002-01-01
影响因子：
4.5
通讯作者：
Slavin, J
中科院分区：
文献类型：
--
作者：
Bhatia, M;Brady, M;Slavin, J
炎症介质包括趋化因子在急性胰腺炎中起关键作用。然而，胰腺内早期炎症信号的确切性质仍不清楚。我们研究了分离的胰腺腺泡合成CC趋化因子单核细胞趋化蛋白-1（MCP-1）和CXC趋化因子精氨酸诱导的中性粒细胞趋化因子（CINC）的能力，以及对生理和超生理浓度的促分泌素雨蛙素的反应。分离的大鼠胰腺腺泡维持在短期（小于或等于48小时）的原代培养组成型合成MCP-1和CINC。雨蛙肽（10（-7）M;超最大剂量）增加MCP-1的产生，但不增加CINC。蛙皮素诱导的MCP-1合成增加伴随着EMSA显示的核因子（NF）-kappaB活化增加。用NF-κ B抑制剂N-乙酰半胱氨酸（NAC）和N-甲苯磺酰苯丙氨酸氯甲基酮（TPCK）预处理可阻断雨蛙肽诱导的NF-κ B活化，并消除雨蛙肽对MCP-1合成的影响。用钙拮抗剂BAPTA-AM预处理也能阻断雨蛙肽对MCP-1合成的影响。这些结果表明，分离的腺泡合成MCP-1和CINC，并支持腺泡衍生的趋化因子作为急性胰腺炎炎症反应的早期介质的想法。尽管雨蛙肽过度刺激通过涉及NF-κ B激活的钙依赖性机制增加MCP-1合成，但CINC合成不受影响。这表明腺泡细胞内CC和CXC趋化因子的调节可能是完全不同的。
Inflammatory mediators including chemokines play a critical role in acute pancreatitis. The precise nature of early inflammatory signals within the pancreas remains, however, unclear. We examined the ability of isolated pancreatic acini to synthesize CC chemokine monocyte chemotactic protein-1 (MCP-1) and CXC chemokine cytokine-induced neutrophil chemoattractant (CINC) and the response to the secretagogue cerulein at physiological and supraphysiological concentrations. Isolated rat pancreatic acini maintained in short-term (less than or equal to 48 h) primary culture constitutively synthesized MCP-1 and CINC. Cerulein (10(-7) M; supramaximal dose) increased production of MCP-1 but not CINC. Cerulein-induced increase in MCP-1 synthesis was accompanied by increase in nuclear factor (NF)-kappaB activation shown by EMSA. Pretreatment with NF-kappaB inhibitors N-acetylcysteine (NAC) and N-tosylphenyalanine chloromethyl ketone (TPCK) blocked cerulein-induced NF-kappaB activation and abolished cerulein's effect on MCP-1 synthesis. Pretreatment with calcium antagonist BAPTA-AM also blocked cerulein's effect on MCP-1 synthesis. These results indicate that isolated acini synthesize MCP-1 and CINC and support the idea of acinar-derived chemokines as early mediators of inflammatory response in acute pancreatitis. Although cerulein hyperstimulation increased MCP-1 synthesis by a calcium-dependent mechanism involving NF-kappaB activation, CINC synthesis was not affected. This suggests that regulation of CC and CXC chemokines within acinar cells may be quite different.