Interleukin 11 signaling in 3T3-L1 adipocytes.
Interleukin 11 (IL-11) is an anti-inflammatory cytokine with receptors located on most cell types and tissues throughout the body. Its anti-inflammatory properties are mediated through suppression of cytokine synthesis, in large part by prevention of NF-kappaB activation. As adipose tissue synthesizes and secretes cytokines involved in establishing insulin resistance and due to the ability of IL-11 to suppress cytokine synthesis, we initiated an investigation to determine the signal transduction pathways initiated by IL-11 in adipose tissue. Using the 3T3-L1 adipocyte cell culture model we demonstrate the rapid activation of the p44/42MAP kinase, PI3-kinase, and STATs 1 and 3. Activation of MAP kinase is demonstrated to lead to the downstream activation of p90 RSK (ribosomal S6 kinase) as well as ATF-1 and CREB. PI3-kinase appears to activate the downstream target of p70 S6 kinase resulting in phosphorylation of ribosomal protein S6. STAT phosphorylation appears to be initiated through PI3-kinase and to a lesser degree through p44/42 MAP kinase. These studies demonstrate the activation of three major signaling pathways and support a role for IL-11 in the regulation of both transcription and protein synthesis in fully differentiated adipocytes.
Tenney
Raleigh
R
Department of Biochemistry and Molecular Biology, The Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA.
Stansfield
Karrie
K
Pekala
Phillip H
PH
D041721:3T3-L1 Cells; D051697:Activating Transcription Factor 1; D017667:Adipocytes / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005809:Genes, Regulator / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D017370:Interleukin-11 / Q000378:metabolism*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D051697:Activating Transcription Factor 1; C497100:Atf1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D017370:Interleukin-11; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D048052:Mitogen-Activated Protein Kinase 3