Inhibition of lymphocyte apoptosis by pancreatic stellate cells: impact of interleukin-15.
There is growing evidence that pancreatic stellate cells (PSCs) produce cytokines and take part in the regulation of inflammatory processes in the pancreas. IL-15 inhibits apoptosis of various cell populations. This study was performed to investigate whether PSCs produce IL-15 and thereby can affect lymphocytes. Primary PSCs were isolated from the rat pancreas using density gradient centrifugation. mRNA expression of IL-15 was demonstrated by RT-PCR, and IL-15 protein was analyzed by immunoblotting. Lymphocytes obtained from rat mesenterial lymph nodes were cocultured with in vitro activated PSCs. Apoptosis has been quantified by the binding of annexin V-FITC with a flow cytometer. Proliferation was monitored using [3H]thymidine incorporation. PSCs express two splice variants of IL-15. The protein was detectable only in cell lysates but not in the cell culture supernatant. Cocultivation of lymphocytes with PSCs and IL-15 inhibited spontaneous lymphocyte apoptosis, and this effect was reduced by an anti-IL-15 antibody. Lymphocytes induced vice versa the proliferation and collagen production of PSCs. The inhibition of spontaneous lymphocyte apoptosis in cocultures with PSCs was at least partially mediated by cell-bound IL-15. This effect and the stimulation of PSCs by lymphocytes may lead to a circulus vitiosus, resulting in the persistence of inflammatory processes and the development of fibrosis during chronic pancreatitis.
Sparmann
Gisela
G
Division of Gastroenterology, Department of Medicine, University of Rostock, D-18057 Rostock, Germany. gisela.sparmann@med.uni-rostock.de
Glass
Anne
A
Brock
Peter
P
Jaster
Robert
R
Koczan
Dirk
D
Thiesen
Hans-Jürgen
HJ
Liebe
Stefan
S
Emmrich
Jörg
J
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D015870:Gene Expression; D020869:Gene Expression Profiling; D019409:Interleukin-15 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew
D019409:Interleukin-15