Regulation of p38 MAPK and glucocorticoid receptor activation by hydrocortisone in mono-and co-cultured pancreatic acinar and stellate cells

被引:6
作者
Blauer, Merja [1 ,2 ,3 ]
Sand, Juhani [1 ,2 ,3 ]
Laukkarinen, Johanna [1 ,2 ,3 ]
机构
[1] Tampere Univ Hosp, Tampere Pancreas Lab, Tampere, Finland
[2] Tampere Univ Hosp, Dept Gastroenterol & Alimentary Tract Surg, Teiskontie 35, FIN-33521 Tampere, Finland
[3] Tampere Univ, Fac Med & Hlth Technol, Tampere, Finland
关键词
Acute pancreatitis; Glucocorticoids; Inflammation; Paracrine interaction; Prophylactic; SIGNAL-TRANSDUCTION; PROTEIN-KINASES; RAT; DEXAMETHASONE; INHIBITION; STRESS; EXPRESSION; MECHANISM; TISSUE; MODEL;
D O I
10.1016/j.pan.2020.12.024
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/objectives: Acute pancreatitis develops as an inflammatory response to pancreatic tissue injury. Postoperative pancreatitis has recently been associated with increased occurrence of complications. Activation of the mitogen-activated protein kinase p38 (p38 MAPK) pathway occurs early in acute pancreatitis and its inhibition has been suggested to alleviate pancreatic inflammation. Glucocorticoids are potent anti-inflammatory steroids whose use in the management of acute pancreatitis remains controversial. Our aim was to examine the effect of crosstalk between pancreatic acinar cells (PACs) and stellate cells (PSCs) on p38 MAPK and glucocorticoid receptor (GR) activation and to assess the impact of hydrocortisone on these events. Methods: The long-term co-culture setting for mouse PACs and PSCs developed in our laboratory was used. Parallel 4d mono- and co-cultures with or without 10 nM hydrocortisone were performed followed by immunocytochemical analysis of nuclear GR and phospho-p38 MAPK (pp38 MAPK). Results: Hydrocortisone inhibited pp38 MAPK up-regulation evoked by co-culture in PACs and PSCs and increased nuclear translocation of GR in PAC monocultures and in co-cultured PACs and PSCs. In PSC monocultures and co-cultured PACs, ligand-independent expression of nuclear GR was observed. In the former no change in nuclear GR but a significant decrease in total GR as analyzed by Western blot was caused by hydrocortisone. Conclusions: Cellular microenvironment plays a significant role on p38 MAPK and GR activation in PACs and PSCs. Hydrocortisone is an effective means to inhibit p38 MAPK activation in PACs and PSCs. Both ligand-dependent and -independent regulatory roles for GR are suggested in the exocrine pancreas. (C) 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:384 / 389
页数:6
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