Nuclear expression of interleukin-33 in pancreatic stellate cells.
Activated pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis in chronic pancreatitis and pancreatic cancer. Recent studies have suggested a role of IL-33, a newly identified IL-1 family member, in fibrosis. We here examined the expression of IL-33 and the IL-33-mediated regulation of cell functions in PSCs. PSCs were isolated from human and rat pancreas tissues. The expression of IL-33 was examined by Western blotting, PCR, ELISA, and immunostaining. The roles of IL-33 in the regulation of PSC functions were examined by using recombinant IL-33 and small interfering RNA. Activated PSCs expressed IL-33 in the nucleus, and the expression was increased by IL-1β, TNF-α, PDGF-BB, and IFN-γ, but not TGF-β1. Nuclear IL-33 expression was also observed in the pancreatic acinar and ductal cells. IL-1β induced IL-33 expression mainly through the activation of NF-κB and ERK pathways and partially through that of p38 MAP kinase, whereas PDGF-BB induced IL-33 expression mainly through the activation of ERK pathway. PSCs expressed soluble ST2, ST2L, and IL-1RAcP, but the expression level of ST2L was relatively low. Recombinant IL-33 did not stimulate key cell functions of PSCs. Decreased IL-33 expression by small interfering RNA resulted in decreased proliferation in response to PDGF-BB. In conclusion, activated PSCs expressed IL-33 in the nucleus. IL-33 might regulate the PDGF-induced proliferation in PSCs.
Masamune
Atsushi
A
Tohoku Univ. Graduate School of Medicine, Sendai, Japan. amasamune@med.tohoku.ac.jp
Watanabe
Takashi
T
Kikuta
Kazuhiro
K
Satoh
Kennichi
K
Kanno
Atsushi
A
Shimosegawa
Tooru
T
D000818:Animals; D000077214:Becaplermin; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017208:Rats, Wistar; D018123:Receptors, Interleukin / Q000378:metabolism; D015398:Signal Transduction
C506536:IL33 protein, human; C553108:Il33 protein, rat; D007375:Interleukin-1; D000067596:Interleukin-33; D007378:Interleukins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D034741:RNA, Small Interfering; D018123:Receptors, Interleukin; D000077214:Becaplermin