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Adiponectin-stimulated CXCL8 release in primary human hepatocytes is regulated by ERK1/ERK2, p38 MAPK, NF-kappaB, and STAT3 signaling pathways
- Source :
- American journal of physiology. Gastrointestinal and liver physiology. 297(3)
- Publication Year :
- 2009
-
Abstract
- Adiponectin is believed to exert hepatoprotective effects and induces CXCL8, a chemokine that functions as a survival factor, in vascular cells. In the current study, it is demonstrated that adiponectin also induces CXCL8 expression in primary human hepatocytes but not in hepatocellular carcinoma cell lines. Knock down of the adiponectin receptor (AdipoR) 1 or AdipoR2 by small-interfering RNA indicates that AdipoR1 is involved in adiponectin-stimulated CXCL8 release. Adiponectin activates nuclear factor (NF)-κB in primary hepatocytes and pharmacological inhibition of NF-κB, the p38 mitogen-activated protein kinase, and extracellular signal-regulated kinase (ERK) 1/ERK2 reduces adiponectin-mediated CXCL8 secretion. Furthermore, adiponectin also activates STAT3 involved in interleukin (IL)-6 and leptin-mediated CXCL8 induction in primary hepatocytes. Inhibition of JAK2 by AG-490 does not abolish adiponectin-stimulated CXCL8, indicating that this kinase is not involved. Pretreatment of primary cells with “STAT3 Inhibitor VI,” however, elevates hepatocytic CXCL8 secretion, demonstrating that STAT3 is a negative regulator of CXCL8 in these cells. In accordance with this assumption, IL-6, a well-characterized activator of STAT3, reduces hepatocytic CXCL8. Therefore, adiponectin-stimulated induction of CXCL8 seems to be tightly controlled in primary human hepatocytes, whereas neither NF-κB, STAT3, nor CXCL8 are influenced in hepatocytic cell lines. CXCL8 is a survival factor, and its upregulation by adiponectin may contribute to the hepatoprotective effects of this adipokine.
- Subjects :
- musculoskeletal diseases
STAT3 Transcription Factor
Chemokine
Time Factors
Physiology
p38 mitogen-activated protein kinases
Cell Culture Techniques
p38 Mitogen-Activated Protein Kinases
Downregulation and upregulation
Physiology (medical)
Cell Line, Tumor
Humans
Interleukin 8
RNA, Messenger
Phosphorylation
STAT3
Protein Kinase Inhibitors
Adiponectin receptor 1
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Hepatology
Adiponectin
biology
Interleukin-8
Gastroenterology
NF-kappa B
Recombinant Proteins
Up-Regulation
biology.protein
Cancer research
Hepatocytes
RNA Interference
Signal transduction
Receptors, Adiponectin
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
Subjects
Details
- ISSN :
- 15221547
- Volume :
- 297
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Accession number :
- edsair.doi.dedup.....412aa6162977db280cb71ffeba3ce685