title: Pancreatic stellate cells and CX3CR1: occurrence in normal pancreas and acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist.
abstract: OBJECTIVE
  Numerous studies suggest important roles of the chemokine, fractalkine (CX3CL1), in acute/chronic pancreatitis; however, the possible mechanisms of the effects are unclear. Pancreatic stellate cells (PSCs) can play important roles in pancreatitis, secreting inflammatory cytokines/chemokines, as well as proliferation. Therefore, we investigated CX3CL1 receptor (CX3CR1) occurrence in normal pancreas and pancreatitis (acute/chronic) tissues and the effects of CX3CL1 on activated PSCs.
  
  
  METHODS
  CX3CR1 expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues was evaluated with immunohistochemical analysis. CX3CR1 expression and effects of CX3CL1 on activated PSCs were examined with real-time polymerase chain reaction, BrdU (5-bromo-2-deoxyuridine) assays, and Western blotting.
  
  
  RESULTS
  In normal pancreas, acinar cells expressed CX3CR1 within granule-like formations in the cytoplasm, whereas in acute/chronic pancreatitis, acinar, ductal, and activated PSCs expressed CX3CR1 on cell membranes. With activation of normal PSCs, CX3CR1 is increased. CX3CL1 activated multiple signaling cascades in PSCs. CX3CL1 did not induce inflammatory genes expression in activated PSCs, but induced proliferation.
  
  
  CONCLUSIONS
  CX3CR1s are expressed in normal pancreas. Expression is increased in acute/chronic pancreatitis, and the CX3CR1s are activated. CX3CL1 induces proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest that CX3CR1 activation of PSCs could be important in their effects in pancreatitis, especially to PSC proliferation in pancreatitis where CX3CL1 levels are elevated.
authors.affiliation: From the *Department of Medicine and Bioregulatory Science, Kyushu University, Fukuoka, Japan; †Department of Cell Biology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; and ‡Department of Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Uchida
authors.forename: Tetsuhide
authors.initials: T
authors.lastname: Ito
authors.forename: Taichi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hijioka
authors.forename: Hisato
authors.initials: H
authors.lastname: Igarashi
authors.forename: Takamasa
authors.initials: T
authors.lastname: Oono
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Robert T
authors.initials: RT
authors.lastname: Jensen
mesh_terms: D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D000073883:CX3C Chemokine Receptor 1; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism / Q000494:pharmacology; D054428:Chemokine CX3CL1 / Q000494:pharmacology; D015870:Gene Expression; D007150:Immunohistochemistry; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D058954:Pancreatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D010195:Pancreatitis / Q000235:genetics / Q000378:metabolism; D050500:Pancreatitis, Chronic / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D019707:Receptors, Chemokine / Q000819:agonists / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; D019707:Receptors, Chemokine