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Regulation of pancreatic inflammation by connective tissue growth factor ( CTGF / CCN 2)
Author(s) -
Charrier Alyssa,
Chen Ruju,
Kemper Sherri,
Brigstock David R.
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12215
Subject(s) - ctgf , connective tissue , inflammation , growth factor , medicine , pathology , receptor
Summary Pancreatitis is caused by long‐term heavy alcohol consumption, which results in injury and death of pancreatic acinar cells ( PAC ). The PAC play a pivotal role in mediating early inflammatory responses but the underlying mechanisms remain poorly understood. Treatment of C57BL/6 mice with ethanol and cerulein resulted in increased staining for acinar interleukin‐1 β (IL‐1 β ), chemokine (C‐C motif) ligand 3 ( CCL3 ), or connective tissue growth factor ( CTGF / CCN 2) by Day 16 and this was associated with increased infiltration of F4/80‐positive macrophages and increased expression of pancreatic CTGF / CCN 2 mRNA . Compared with wild‐type Swiss Webster mice, ethanol treatment of pan‐green fluorescent protein ( GFP )‐ CTGF / CCN2 transgenic mice caused enhanced acinar staining for GFP or CTGF / CCN2 and a significant increase in pancreatic infiltration of F4/80‐positive macrophages or NIMP ‐R14‐positive neutrophils. Treatment of primary mouse PAC or the rat AR 42J PAC line with ethanol or CTGF / CCN 2 resulted in enhanced expression of IL‐1 β or CCL 3. Conditioned medium from CTGF / CCN 2‐treated AR 42J cells induced chemotaxis in NR 8383 macrophages and this response was abrogated in a dose‐dependent manner by addition of BX 471, an inhibitor of chemokine (C‐C motif) receptor 1. These results reveal that acinar CTGF / CCN 2 plays a novel role in alcohol‐induced inflammatory processes in the pancreas by increasing infiltration of macrophages and neutrophils and increasing acinar production of inflammatory mediators such as IL ‐1 β or CCL 3. The early production of CTGF / CCN 2 by PAC to drive inflammation is distinct from its previously reported production by pancreatic stellate cells to drive fibrosis at later stages of pancreatic injury.