Adiponectin stimulates proliferation and cytokine secretion in colonic epithelial cells

Regul Pept. 2006 May 15;134(2-3):105-13. doi: 10.1016/j.regpep.2006.02.001. Epub 2006 Mar 10.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / physiology*
  • Cell Proliferation / drug effects*
  • Chemokine CCL2 / metabolism
  • Cytokines / metabolism*
  • Drug Synergism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flavonoids / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • HT29 Cells
  • Humans
  • Imidazoles / pharmacology
  • Indoles / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-8 / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Isoquinolines / pharmacology
  • Maleimides / pharmacology
  • NF-kappa B / metabolism
  • Nitriles / pharmacology
  • Phosphorylation / drug effects
  • Pyridines / pharmacology
  • Sulfonamides / pharmacology
  • Sulfones / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 3-(4-methylphenylsulfonyl)-2-propenenitrile
  • Adiponectin
  • CCL2 protein, human
  • Chemokine CCL2
  • Cytokines
  • Flavonoids
  • Imidazoles
  • Indoles
  • Interleukin-1
  • Interleukin-8
  • Isoquinolines
  • Maleimides
  • NF-kappa B
  • Nitriles
  • Pyridines
  • Sulfonamides
  • Sulfones
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • bisindolylmaleimide I
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one