PMID- 18661119
OWN - NLM
STAT- MEDLINE
DCOM- 20090112
LR  - 20211020
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 51
IP  - 10
DP  - 2008 Oct
TI  - CD40 activation in human pancreatic islets and ductal cells.
PG  - 1853-61
LID - 10.1007/s00125-008-1092-y [doi]
AB  - AIMS/HYPOTHESIS: CD40 expression on non-haematopoietic cells is linked to 
      inflammation. We previously reported that CD40 is expressed on isolated human and 
      non-human primate islets and its activation results in secretion of IL-8, 
      macrophage inflammatory protein 1-beta (MIP-1beta) and monocyte chemoattractant 
      protein-1 (MCP-1) through nuclear factor-kappaB and extracellularly regulated 
      kinases 1/2 pathways. The objective of this study was to identify the pattern of 
      gene expression, and to study viability and functionality affected by CD40-CD40 
      ligand (CD40L) interaction in human islets. Furthermore, we have studied the 
      CD40-mediated cytokine/chemokine profile in pancreatic ductal cells, as they are 
      always present in human islet transplant preparations and express CD40 
      constitutively. METHODS: CD40-CD40L gene expression modulation was studied by 
      microarray on islet cells depleted of ductal cells. Selected genes were validated 
      by quantitative RT-PCR. The cytokine profile in purified ductal cells was 
      evaluated by Luminex technology, based on the use of fluorescent-coated beads, 
      known as microspheres, and capable of multiplex detection of proteins from a 
      single sample. Glucose-stimulated insulin secretion and islet viability were 
      assessed by perifusion and 7-aminoactinomycin D membrane exclusion, respectively. 
      RESULTS: Statistical analysis of microarrays identified 30 genes exhibiting at 
      least a 2.5-fold increase across all replicate arrays. The majority of them were 
      related to oxidative stress/inflammation. Prominently upregulated were chemokine 
      C-X-C motif ligand 1 (CXCL1), CXCL2 and CXCL3 belonging to the CXC family of 
      chemokines related to IL-8. CD40-mediated CXCL1 secretion was confirmed by ELISA. 
      The viability or in vitro function was not affected by CD40 activation. In 
      addition to previously reported IL-8, MIP-1beta and MCP-1, CD40 stimulation in 
      ductal cells produced IL-1beta, IFN-gamma, TNF-alpha, granulocyte 
      colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. 
      CONCLUSIONS/INTERPRETATION: CD40 activation in islets and ductal cells produces 
      cytokines/chemokines with a broad-spectrum range of biological functions.
FAU - Klein, D
AU  - Klein D
AD  - Diabetes Research Institute, Leonard M. Miller School of Medicine, University of 
      Miami, 1450 NW 10th Avenue, Miami, FL 33136, USA.
FAU - Timoneri, F
AU  - Timoneri F
FAU - Ichii, H
AU  - Ichii H
FAU - Ricordi, C
AU  - Ricordi C
FAU - Pastori, R L
AU  - Pastori RL
LA  - eng
GR  - 5U42 RR 016603/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080726
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (CD40 Antigens)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - Adult
MH  - CD40 Antigens/genetics/*metabolism/physiology
MH  - CD40 Ligand/genetics/metabolism/physiology
MH  - Cell Survival
MH  - Chemokine CXCL1/metabolism
MH  - Chemokines/metabolism
MH  - Cytokines/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Humans
MH  - Islets of Langerhans/cytology/*metabolism
MH  - Middle Aged
MH  - Oligonucleotide Array Sequence Analysis
MH  - Pancreatic Ducts/cytology/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Young Adult
EDAT- 2008/07/29 09:00
MHDA- 2009/01/13 09:00
CRDT- 2008/07/29 09:00
PHST- 2008/03/06 00:00 [received]
PHST- 2008/06/09 00:00 [accepted]
PHST- 2008/07/29 09:00 [pubmed]
PHST- 2009/01/13 09:00 [medline]
PHST- 2008/07/29 09:00 [entrez]
AID - 10.1007/s00125-008-1092-y [doi]
PST - ppublish
SO  - Diabetologia. 2008 Oct;51(10):1853-61. doi: 10.1007/s00125-008-1092-y. Epub 2008 
      Jul 26.