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Expression and function of interleukin‐6 in epithelial cells
Author(s) -
Krueger James,
Ray Anuradha,
Tamm Igor,
Sehgal Pravinkumar B.
Publication year - 1991
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240450404
Subject(s) - microbiology and biotechnology , biology , transfection , cell culture , cell growth , stromal cell , chemistry , cancer research , genetics
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 I, −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 hyperprolifer active (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.