Expression and function of interleukin-6 in epithelial cells

✍ Scribed by James Krueger; Anuradha Ray; Igor Tamm; Pravinkumar B. Sehgal

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 714 KB
• Volume: 45
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240450404

✦ Synopsis

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, -1 73 to -151 and MRE 11, -158 to -145). MRE I contains the typical GACGTCA cAMPand phorbol ester-responsive (CREDRE) motif, whereas MRE I1 defines a new CREDRE 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.