Expression and function of interleukin-6 in epithelial cells.
Epithelial cells both produce and are affected by interleukin-6 (IL-6). Experiments with an adenocarcinoma-derived cell line (HeLa) reveal that activation of the transfected human IL-6 promoter occurs largely through two partially overlapping second messenger (cAMP, phorbol ester)- and cytokine (IL-1, TNF, serum)-responsive enhancer elements (MRE 1, -173 to -151 and MRE II, -158 to -145). MRE I contains the typical GACGTCA cAMP and phorbol ester-responsive (CRE-TRE) motif, whereas MRE II defines a new CRE/TRE motif that contains an imperfect dyad repeat. The mechanism of dexamethasone-mediated repression of IL-6 gene expression in epithelial cells involves occlusion of the entire MRE enhancer region and of the core-promoter elements (TATA-box and RNA start site) by ligand-activated glucocorticoid receptor. Enhanced levels of IL-6 expression are observed in many solid tumors and in the hyperproliferative (and glucocorticoid-suppressible) lesions of psoriasis. In cell culture, IL-6 enhances, inhibits, or has no effect on the proliferation of epithelial cells depending upon the cell-type examined. IL-6 enhances proliferation of keratinocytes but inhibits that of breast carcinoma cell lines ZR-75-1 and T-47D. In these breast carcinoma cells, IL-6 elicits a major change in cell phenotype which is characterized by a fibroblastoid morphology, enhanced motility, increased cell-cell separation, and decreased adherens type junctions (desmosomes and focal adhesions). The new data identify IL-6 as a regulator of epithelial cell growth and of cell-cell association.
Krueger
J
J
Rockefeller University, New York, New York 10021.
Ray
A
A
Tamm
I
I
Sehgal
P B
PB
D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000276:immunology; D004247:DNA; D004848:Epithelium / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000502:physiology; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology; D011565:Psoriasis / Q000276:immunology
D015850:Interleukin-6; D004247:DNA