Induction of chemokines in rat pancreatic acinar cell injury.
BACKGROUND
The pathogenesis of chronic pancreatitis (CP), especially of acinar cell injury, is still unclear. Interleukin (IL)-8 is a chemokine that is involved in various inflammatory diseases.


OBJECTIVE
To examine whether IL-8 and other chemokines are expressed in experimental acinar cell injury.


METHODS
IL-8 expression was analyzed in spontaneous CP in the WBN/Kob rat and in rat pancreatic acinar AR4-2J cells treated with various stimuli using reverse transcription-polymerase chain reaction (semiquantitative) and immunohistochemistry.


RESULTS
Chronic pancreatitis developed at 12 weeks in the WBN/Kob rats. IL-8, macrophage chemoattractant protein-1, and macrophage inflammatory protein-2 mRNA was expressed from 4 weeks and peaked at 12 weeks. Immunohistochemistry showed a strong expression of IL-8 in acinar cells, proliferating ductular cells, and interstitial infiltrating cells. In contrast, normal pancreatic tissues lacked IL-8 expression. Further, IL-8 mRNA and protein were detectable in AR4-2J cells treated with the various stimuli, such as menadione, tumor necrosis factor-alpha and transforming growth factor beta1.


CONCLUSIONS
These results suggest that IL-8 is expressed in the pancreatic parenchyma and infiltrates in CP and that it plays a role in the initial pathogenesis of CP together with other chemokines and cytokines.
Xie
Min-Jue
MJ
Department of Internal Medicine and Medical Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan.
Motoo
Yoshiharu
Y
Su
Shi-Bing
SB
Mouri
Hisatsugu
H
Sawabu
Norio
N
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics; D002908:Chronic Disease; D004195:Disease Models, Animal; D015870:Gene Expression / Q000276:immunology; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000032:analysis / Q000235:genetics*; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010179:Pancreas / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016209:Interleukin-8; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat