Abstract
Adiponectin is a recently described mediator secreted by adipose tissue. Here we report the growth promoting and pro-inflammatory actions of adiponectin on colonic epithelial cancer cells. Full-length and globular adiponectin produced an identical stimulation of HT-29 cell growth that was blocked by inhibition of adenylate cyclase and protein kinase A and partially inhibited by a pan-specific protein kinase C inhibitor, but was unaffected by specific inhibition of extracellular signal-related kinase (ERK) or p38 MAP kinase. Globular adiponectin but not full-length adiponectin significantly increased the secretion and mRNA levels of IL-8, GM-CSF and MCP-1. Globular adiponectin doubled IL-1beta-stimulated IL-8 and GM-CSF secretion. Adiponectin-stimulated cytokine secretion was blocked by pharmacological inhibitors of NF-kappaB, ERK and p38 MAP kinase. Globular adiponectin increased phosphorylation of both ERK and p38 MAP kinase and increased the nuclear translocation of active NF-kappaB. Adiponectin has pro-proliferative and pro-inflammatory actions on colonic epithelial cells; these appear to be differentially activated by the adiponectin isoforms. Adiponectin may have a role in the regulation of gastrointestinal mucosal function, inflammation and colon carcinogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adiponectin / physiology*
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Cell Proliferation / drug effects*
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Chemokine CCL2 / metabolism
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Cytokines / metabolism*
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Drug Synergism
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Flavonoids / pharmacology
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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HT29 Cells
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Humans
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Imidazoles / pharmacology
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Indoles / pharmacology
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Interleukin-1 / pharmacology
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Interleukin-8 / metabolism
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Intestinal Mucosa / cytology
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Intestinal Mucosa / drug effects*
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Intestinal Mucosa / metabolism
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Isoquinolines / pharmacology
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Maleimides / pharmacology
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NF-kappa B / metabolism
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Nitriles / pharmacology
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Phosphorylation / drug effects
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Pyridines / pharmacology
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Sulfonamides / pharmacology
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Sulfones / pharmacology
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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3-(4-methylphenylsulfonyl)-2-propenenitrile
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Adiponectin
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CCL2 protein, human
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Chemokine CCL2
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Cytokines
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Flavonoids
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Imidazoles
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Indoles
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Interleukin-1
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Interleukin-8
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Isoquinolines
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Maleimides
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NF-kappa B
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Nitriles
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Pyridines
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Sulfonamides
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Sulfones
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Granulocyte-Macrophage Colony-Stimulating Factor
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases
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bisindolylmaleimide I
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
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SB 203580
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one