PMID- 30287405
OWN - NLM
STAT- MEDLINE
DCOM- 20190812
LR  - 20230617
IS  - 1879-260X (Electronic)
IS  - 0925-4439 (Linking)
VI  - 1865
IP  - 1
DP  - 2019 Jan
TI  - TLR4 triggered complex inflammation in human pancreatic islets.
PG  - 86-97
LID - S0925-4439(18)30365-X [pii]
LID - 10.1016/j.bbadis.2018.09.030 [doi]
AB  - Type 2 Diabetes (T2D) is strongly associated with obesity and inflammation. 
      Toll-like receptor-4 (TLR-4) is the major pro-inflammatory pathway with its 
      ligands and downstream products increased systemically in T2D and in at-risk 
      individuals. Detailed mechanisms of the complex proinflammatory response in 
      pancreatic islets remain unknown. In isolated human islets LPS induced IL-1beta, 
      IL-6, IL-8 and TNF production in a TLR4-dependent manner and severely impaired 
      beta-cell survival and function. IL-6 antagonism improved beta-cell function. IL-8, 
      which was identified specifically in alpha-cells, initiated monocyte migration, a 
      process fully blocked by IL-8 neutralization. The TLR4 response was potentiated 
      in obese donors; with higher IL-1beta, IL-6 and IL-8 expression than in non-obese 
      donors. TLR4 activation leads to a complex multi-cellular inflammatory response 
      in human islets, which involves beta-cell failure, cytokine production and 
      macrophage recruitment to islets. In obesity, the amplified TLR4 response may 
      potentiate beta-cell damage and accelerate diabetes progression.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - He, Wei
AU  - He W
AD  - University of Bremen, Center for Biomolecular Interactions Bremen, Germany. 
      Electronic address: hewei@uni-bremen.de.
FAU - Rebello, Osmond
AU  - Rebello O
AD  - University of Bremen, Center for Biomolecular Interactions Bremen, Germany.
FAU - Savino, Rocco
AU  - Savino R
AD  - Department of Health Sciences, Magna Graecia University, Catanzaro, Italy.
FAU - Terracciano, Rosa
AU  - Terracciano R
AD  - Department of Health Sciences, Magna Graecia University, Catanzaro, Italy.
FAU - Schuster-Klein, Carole
AU  - Schuster-Klein C
AD  - ADIR - Groupe de Recherche Servier, Suresnes, France.
FAU - Guardiola, Beatrice
AU  - Guardiola B
AD  - ADIR - Groupe de Recherche Servier, Suresnes, France.
FAU - Maedler, Kathrin
AU  - Maedler K
AD  - University of Bremen, Center for Biomolecular Interactions Bremen, Germany. 
      Electronic address: kmaedler@uni-bremen.de.
LA  - eng
GR  - U24 DK098085/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181001
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Basis Dis
JT  - Biochimica et biophysica acta. Molecular basis of disease
JID - 101731730
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Insulin)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
MH  - Apoptosis
MH  - Cell Movement
MH  - Chemokines/metabolism
MH  - Cytokines/metabolism
MH  - Diabetes Mellitus, Type 2/etiology/*metabolism
MH  - Disease Progression
MH  - Gene Expression Regulation
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Insulin/metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - Islets of Langerhans/*metabolism
MH  - Macrophages/metabolism
MH  - Obesity/complications/*metabolism
MH  - Toll-Like Receptor 4/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Chemokine
OT  - Cytokine
OT  - Inflammation
OT  - Insulin
OT  - Obesity
OT  - TLR4
OT  - Type 2 diabetes
OT  - alpha-Cells
OT  - beta-Cells
EDAT- 2018/10/06 06:00
MHDA- 2019/08/14 06:00
CRDT- 2018/10/06 06:00
PHST- 2018/03/19 00:00 [received]
PHST- 2018/09/06 00:00 [revised]
PHST- 2018/09/20 00:00 [accepted]
PHST- 2018/10/06 06:00 [pubmed]
PHST- 2019/08/14 06:00 [medline]
PHST- 2018/10/06 06:00 [entrez]
AID - S0925-4439(18)30365-X [pii]
AID - 10.1016/j.bbadis.2018.09.030 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Basis Dis. 2019 Jan;1865(1):86-97. doi: 
      10.1016/j.bbadis.2018.09.030. Epub 2018 Oct 1.