PMID- 23447644
OWN - NLM
STAT- MEDLINE
DCOM- 20131231
LR  - 20130520
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 98
IP  - 3
DP  - 2013 Jun 1
TI  - Extracellular HSP60 induces inflammation through activating and up-regulating 
      TLRs in cardiomyocytes.
PG  - 391-401
LID - 10.1093/cvr/cvt047 [doi]
AB  - AIMS: The molecular events leading from cardiomyocyte ischaemia to inflammatory 
      cytokine production are not well understood. We previously found that heat shock 
      protein 60 (HSP60) appeared in extracellular space after cardiomyocyte ischaemia. 
      This study examined the activation and regulation of toll-like receptors (TLRs) 
      by HSP60 in cardiomyocytes. METHODS AND RESULTS: Cytokine production and TLRs 
      regulation mediated by TLRs signalling were examined in response to exogenous 
      HSP60 (exHSP60) and endogenous HSP60 (enHSP60) released extracellularly under 
      ischaemia. The results showed that exHSP60 induced inflammatory cytokine 
      production in adult rat cardiomyocytes and H9c2 cells (a standard cardiac cell 
      line derived from embryonic cells), through a pathway dependent on TLR4, myeloid 
      differentiation factor 88 (MyD88), p38, and nuclear factor-kappaB (NF-kappaB). Further 
      study revealed up-regulated expression of both TLR2 and TLR4 by exHSP60, which 
      was dependent on the activation of TLR4, MyD88, c-Jun NH2-terminal kinase (JNK), 
      and NF-kappaB, but not on p38. In myocytes exposed to ischaemia, enHSP60 was released 
      into the media, and triggered cytokine production and TLR2/4 overexpression, 
      through the same pathways as exHSP60. In rats subjected to LAD ligation, the 
      released enHSP60 contributed to cytokine production and TLR2/4 overexpression in 
      the ischaemic myocardium. CONCLUSION: Extracellular HSP60 induces cytokine 
      production via TLR4-MyD88-p38/NF-kappaB pathway, and up-regulates TLR2/4 expression 
      via TLR4-MyD88-JNK/NF-kappaB pathway. Both pathways contribute to myocardial 
      inflammation induced by ischaemia.
FAU - Tian, Jing
AU  - Tian J
AD  - Department of Physiology and the Key Laboratory of Molecular Neurobiology of 
      Ministry of Education, Second Military Medical University, 800 Xiangyin Road, 
      Shanghai 200433, PR China.
FAU - Guo, Xin
AU  - Guo X
FAU - Liu, Xue-Mei
AU  - Liu XM
FAU - Liu, Li
AU  - Liu L
FAU - Weng, Qi-Fang
AU  - Weng QF
FAU - Dong, Shu-Juan
AU  - Dong SJ
FAU - Knowlton, Anne A
AU  - Knowlton AA
FAU - Yuan, Wen-Jun
AU  - Yuan WJ
FAU - Lin, Li
AU  - Lin L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130227
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Chaperonin 60)
RN  - 0 (Hspd1 protein, rat)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Myd88 protein, rat)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Tlr2 protein, rat)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chaperonin 60/*metabolism
MH  - Disease Models, Animal
MH  - Inflammation/genetics/immunology/*metabolism
MH  - Inflammation Mediators/metabolism
MH  - Interleukin-6/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Male
MH  - Mitochondrial Proteins/*metabolism
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - Myocardial Ischemia/genetics/immunology/*metabolism
MH  - Myocytes, Cardiac/immunology/*metabolism
MH  - NF-kappa B/metabolism
MH  - RNA Interference
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Time Factors
MH  - Toll-Like Receptor 2/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Toll-Like Receptors/genetics/*metabolism
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - Cardiomyocyte
OT  - Heat shock protein
OT  - Inflammatory cytokine
OT  - Toll-like receptor
EDAT- 2013/03/01 06:00
MHDA- 2014/01/01 06:00
CRDT- 2013/03/01 06:00
PHST- 2013/03/01 06:00 [entrez]
PHST- 2013/03/01 06:00 [pubmed]
PHST- 2014/01/01 06:00 [medline]
AID - cvt047 [pii]
AID - 10.1093/cvr/cvt047 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2013 Jun 1;98(3):391-401. doi: 10.1093/cvr/cvt047. Epub 2013 Feb 
      27.