RGD Reference Report - Adiponectin protects against Toll-like receptor 4-mediated cardiac inflammation and injury. - Rat Genome Database

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Adiponectin protects against Toll-like receptor 4-mediated cardiac inflammation and injury.

Authors: Jenke, A  Wilk, S  Poller, W  Eriksson, U  Valaperti, A  Rauch, BH  Stroux, A  Liu, P  Schultheiss, HP  Scheibenbogen, C  Skurk, C 
Citation: Jenke A, etal., Cardiovasc Res. 2013 Aug 1;99(3):422-31. doi: 10.1093/cvr/cvt118. Epub 2013 May 13.
RGD ID: 8695925
Pubmed: PMID:23674516   (View Abstract at PubMed)
DOI: DOI:10.1093/cvr/cvt118   (Journal Full-text)

AIMS: Adiponectin (APN) is an immunomodulatory and cardioprotective adipocytokine. Toll-like receptor (TLR) 4 mediates autoimmune reactions that cause myocarditis resulting in inflammation-induced cardiac injury. Here, we investigated whether APN inhibits inflammation and injury in autoimmune myocarditis by interfering with TLR4 signalling. METHODS AND RESULTS: APN overexpression in murine experimental autoimmune myocarditis (EAM) down-regulated cardiac expression of TLR4 and its downstream targets tumour necrosis factor (TNF)alpha, interleukin (IL)-6, IL-12, CC chemokine ligand (CCL)2, and intercellular adhesion molecule (ICAM)-1 resulting in reduced infiltration with cluster of differentiation (CD)3+, CD14+, and CD45+ immune cells as well as diminished myocardial apoptosis. Expression of TLR4 signalling pathway components was unchanged in hearts and spleens of APN-knockout (APN-KO) mice. In vitro APN had no effect on TLR4 expression in cardiac and immune cells but induced dissociation of APN receptors from the activated TLR4/CD14 signalling complex. APN inhibited the expression of a TLR4-mediated inflammatory phenotype induced by exogenous and endogenous TLR4 ligands as assessed by attenuated nuclear factor (NF)-kappaB activation and reduced expression of TNFalpha, IL-6, CCL2, and ICAM-1. Accordingly, following TLR4 ligation, splenocytes from APN-KO mice showed enhanced expression of TNFalpha, IL-6, IL-12, CCL2, and ICAM-1, whereas dendritic cells (DCs) from APN-KO mice demonstrated increased activation and T-cell priming capacity. Moreover, APN diminished TLR4-mediated splenocyte migration towards cardiac cells as well as cardiomyocyte apoptosis after co-cultivation with splenocytes. Mechanistically, APN inhibited TLR4 signalling through cyclooxygenase (COX)-2, protein kinase A (PKA), and meiosis-specific serine/threonine kinase (MEK)1. CONCLUSION: Our observations indicate that APN protects against inflammation and injury in autoimmune myocarditis by diminishing TLR4 signalling thereby attenuating inflammatory activation and interaction of cardiac and immune cells.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ADIPOQHumanExperimental Autoimmune Myocarditis  ISOAdipoq (Mus musculus) RGD 
AdipoqRatExperimental Autoimmune Myocarditis  ISOAdipoq (Mus musculus) RGD 
AdipoqMouseExperimental Autoimmune Myocarditis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adipoq  (adiponectin, C1Q and collagen domain containing)

Genes (Mus musculus)
Adipoq  (adiponectin, C1Q and collagen domain containing)

Genes (Homo sapiens)
ADIPOQ  (adiponectin, C1Q and collagen domain containing)


Additional Information