title: Leptin induces an Apc genotype-associated colon epithelial cell chemokine production pattern associated with macrophage chemotaxis and activation.
abstract: Leptin is an adipocyte-derived cytokine associated with obesity and inflammation recently shown to influence colon epithelial cell fate and colon inflammation. Thus, the purpose of this study is to investigate the influences of leptin exposure on the production of proinflammatory signals by a model of normal [YAMC (Apc+/+)] and preneoplastic [IMCE (ApcMin/+)] colon epithelial cells. Here, we characterize the production of specific CC and CXC chemokines by IMCE and YAMC cells using an antibody-based cytokine array. Further, since epithelial cells are hypothesized to be accessory to the inflammatory response, we assessed the ability of supernants from leptin-exposed colon epithelial cells to activate macrophage chemotaxis and nitric oxide production. Both YAMC and IMCE cells produced the following chemokines from the CC family; MCP-1, MIP-3alpha, TCA-3, CTACK and RANTES. These cell lines also produced the following CXC chemokines; MIP-2, CXCL18, KC and LIX. Conditioned media from leptin-treated YAMC and IMCE cells induced nitric oxide production by macrophages (P<0.05). However, only conditioned media from leptin-treated IMCE cells induced macrophage chemotaxis (P<0.05). These data imply that preneoplastic but not normal cells may selectively attract immune cells that promote their survival and transformation. Taken together with our previous data, we conclude that leptin promotes the proliferation of a model of preneoplastic cells (IMCE) and induces the production of chemokines which may activate macrophages and promote macrophage cell chemotaxis. These data provide a rational basis for leptin-induced cross-talk between preneoplastic epithelial cells and immune cells that may influence the promotional phase of carcinogenesis.
authors.affiliation: Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute Bethesda, MD, USA. imigjeni@msu.edu
authors.forename: Jenifer I
authors.initials: JI
authors.lastname: Fenton
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hursting
authors.forename: Susan N
authors.initials: SN
authors.lastname: Perkins
authors.forename: Norman G
authors.initials: NG
authors.lastname: Hord
mesh_terms: D000818:Animals; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D017077:Culture Media, Conditioned; D004847:Epithelial Cells / Q000378:metabolism; D017491:Genes, APC; D005838:Genotype; D020738:Leptin / Q000502:physiology*; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000166:cytology*; D051379:Mice
chemical_list: D018925:Chemokines; D017077:Culture Media, Conditioned; D020738:Leptin