PMID- 20130114
OWN - NLM
STAT- MEDLINE
DCOM- 20100326
LR  - 20161125
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 151
IP  - 3
DP  - 2010 Mar
TI  - Toll-like receptor ligands cause proinflammatory and prodiabetic activation of 
      adipocytes via phosphorylation of extracellular signal-regulated kinase and c-Jun 
      N-terminal kinase but not interferon regulatory factor-3.
PG  - 1097-108
LID - 10.1210/en.2009-1140 [doi]
AB  - Here, we aim to investigate the mechanisms of Toll-like receptor (TLR)-induced 
      prodiabetic and proinflammatory activation of adipocytes and to detect 
      differences in the responsiveness of TLRs to their respective ligands between 
      adipocytes isolated from inflamed vs. noninflamed adipose tissue. Experiments 
      using specific ligands for all known TLRs were performed in murine 3T3-L1 
      adipocytes and in human adipocytes isolated from noninflamed and inflamed adipose 
      tissue. IL-6 and monocyte chemoattractant protein-1 (MCP-1) release were measured 
      by ELISA. The expression of the signal transduction proteins 
      phospho-extracellular signal-regulated kinase (P-Erk), P-c-Jun N-terminal kinase 
      (JNK), and P-interferon regulatory factor-3 was investigated by Western blot 
      analysis. Additionally, functional inhibitors of MAPK kinase-1/-2 and JNK-1/-2 
      were used in the stimulation experiments. Activation of TRL4 by 
      lipopolysaccharide (LPS) and TLR1/2 by Pam(3)Cys up-regulates IL-6 and MCP-1 
      release in adipocytes via specific activation of Erk. Stimulation of adipocytes 
      by macrophage activating lipopeptide-2 (MALP-2) induces MCP-1 but has no effect 
      on IL-6 release. This stimulatory effect on MCP-1 release is antagonized by 
      inhibition of both mitogen-activated protein kinase-1/-2 and JNK-1/-2. 
      Phosphorylation of Erk and JNK is up-regulated after stimulation by MALP-2. In 
      human adipocytes isolated from noninflamed adipose tissue, LPS and Pam(3)Cys, but 
      not MALP-2, are potent inducers of IL-6 and MCP-1. MALP-2 is able to induce IL-6 
      and MCP-1 release in adipocytes isolated from inflamed adipose tissue, whereas 
      these adipocytes lost their ability to respond to LPS. The present results point 
      to a role of the adipose tissue in innate immunity. TLR-ligand-induced 
      proinflammatory and prodiabetic activation of adipocytes might couple visceral 
      adipose tissue dysfunction with insulin resistance and type 2 diabetes mellitus.
FAU - Kopp, Andrea
AU  - Kopp A
AD  - Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, 
      Germany.
FAU - Buechler, Christa
AU  - Buechler C
FAU - Bala, Margarita
AU  - Bala M
FAU - Neumeier, Markus
AU  - Neumeier M
FAU - Scholmerich, Juergen
AU  - Scholmerich J
FAU - Schaffler, Andreas
AU  - Schaffler A
LA  - eng
PT  - Journal Article
DEP - 20100203
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Anthracenes)
RN  - 0 (Butadienes)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Insulin)
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Interleukin-6)
RN  - 0 (Irf3 protein, mouse)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Nitriles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (U 0126)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
SB  - IM
EIN - Endocrinology. 2012 Feb;153(2):1000
MH  - 3T3-L1 Cells
MH  - Adipocytes/*metabolism
MH  - Adipose Tissue/immunology/metabolism
MH  - Adult
MH  - Animals
MH  - Anthracenes
MH  - Butadienes
MH  - Chemokine CCL2/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Humans
MH  - Inflammation/metabolism
MH  - Insulin/metabolism
MH  - Interferon Regulatory Factor-3/metabolism
MH  - Interleukin-6/*metabolism
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Lipopolysaccharides
MH  - MAP Kinase Kinase 1/antagonists & inhibitors/metabolism
MH  - MAP Kinase Kinase 2/antagonists & inhibitors/metabolism
MH  - *MAP Kinase Signaling System
MH  - Male
MH  - Mice
MH  - Myeloid Differentiation Factor 88
MH  - Nitriles
MH  - Phosphorylation
MH  - RNA, Messenger/metabolism
MH  - Toll-Like Receptors/*metabolism
EDAT- 2010/02/05 06:00
MHDA- 2010/03/27 06:00
CRDT- 2010/02/05 06:00
PHST- 2010/02/05 06:00 [entrez]
PHST- 2010/02/05 06:00 [pubmed]
PHST- 2010/03/27 06:00 [medline]
AID - en.2009-1140 [pii]
AID - 10.1210/en.2009-1140 [doi]
PST - ppublish
SO  - Endocrinology. 2010 Mar;151(3):1097-108. doi: 10.1210/en.2009-1140. Epub 2010 Feb 
      3.