PMID- 24512683
OWN - NLM
STAT- MEDLINE
DCOM- 20140602
LR  - 20190816
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 459
IP  - 3
DP  - 2014 May 1
TI  - Chitinase-3-like protein 1 protects skeletal muscle from TNFalpha-induced 
      inflammation and insulin resistance.
PG  - 479-88
LID - 10.1042/BJ20131151 [doi]
AB  - CHI3L1 (chitinase-3-like protein 1) is a glycoprotein consisting of 383 amino 
      acids with a molecular mass of 40 kDa, and its serum level is elevated in 
      inflammatory diseases. Although CHI3L1 is described as a biomarker of 
      inflammation, the function of this protein is not completely understood. In the 
      present study, we examined the regulation of CHI3L1 in primary human skeletal 
      muscle cells. Moreover, we analysed potential autocrine effects of CHI3L1. We 
      show that myotubes express CHI3L1 in a differentiation-dependent manner. 
      Furthermore, pro-inflammatory cytokines up-regulate CHI3L1 expression (6-fold) 
      and release (3-fold). Importantly, CHI3L1 treatment blocked TNFalpha (tumour necrosis 
      factor alpha)-induced inflammation by inhibiting NF-kappaB (nuclear factor kappaB) activation 
      in skeletal muscle cells. We show that this effect is mediated via PAR2 
      (protease-activated receptor 2). In addition, CHI3L1 treatment diminished the 
      TNFalpha-induced expression and secretion of IL (interleukin)-8, MCP1 (monocyte 
      chemoattractant protein 1) and IL-6. In addition, impaired insulin action at the 
      level of Akt and GSK3alpha/beta (glycogen synthase kinase 3alpha/beta) phosphoryl-ation and 
      insulin-stimulated glucose uptake was normalized by CHI3L1. In conclusion, the 
      novel myokine CHI3L1, which is induced by pro-inflammatory cytokines, can 
      counteract TNFalpha-mediated inflammation and insulin resistance in human skeletal 
      muscle cells, potentially involving an auto- and/or para-crine mechanism.
FAU - Gorgens, Sven W
AU  - Gorgens SW
AD  - *Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, 40225 
      Dusseldorf, Germany.
FAU - Eckardt, Kristin
AU  - Eckardt K
AD  - *Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, 40225 
      Dusseldorf, Germany.
FAU - Elsen, Manuela
AU  - Elsen M
AD  - *Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, 40225 
      Dusseldorf, Germany.
FAU - Tennagels, Norbert
AU  - Tennagels N
AD  - daggerR&D Diabetes Division, Sanofi-Aventis Deutschland, 65929 Frankfurt, Germany.
FAU - Eckel, Jurgen
AU  - Eckel J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Adipokines)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CHI3L1 protein, human)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chitinase-3-Like Protein 1)
RN  - 0 (Cytokines)
RN  - 0 (IL6 protein, human)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (Lectins)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptor, PAR-2)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TNF protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Adipokines/genetics/*metabolism
MH  - Adolescent
MH  - Adult
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Chitinase-3-Like Protein 1
MH  - Cytokines/genetics/*metabolism
MH  - Female
MH  - Humans
MH  - *Insulin Resistance
MH  - Interleukin-6/metabolism
MH  - Interleukin-8/metabolism
MH  - Lectins/genetics/*metabolism
MH  - Male
MH  - Muscle Fibers, Skeletal/cytology/immunology/metabolism
MH  - Muscle, Skeletal/cytology/immunology/*metabolism
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Receptor, PAR-2/antagonists & inhibitors/genetics/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/genetics/*metabolism
MH  - *Up-Regulation
MH  - Young Adult
EDAT- 2014/02/12 06:00
MHDA- 2014/06/03 06:00
CRDT- 2014/02/12 06:00
PHST- 2014/02/12 06:00 [entrez]
PHST- 2014/02/12 06:00 [pubmed]
PHST- 2014/06/03 06:00 [medline]
AID - BJ20131151 [pii]
AID - 10.1042/BJ20131151 [doi]
PST - ppublish
SO  - Biochem J. 2014 May 1;459(3):479-88. doi: 10.1042/BJ20131151.