Intracellular production of interleukin-18 in human epithelial-like cell lines is enhanced by hyperosmotic stress in vitro.
Interleukin-18 is a novel multifunctional cytokine, which enhances natural killer cell activity and promotes the induction of cytokine production, including that of interferon-gamma by T cells and antitumor effects. Interleukin-18 is produced by cells of several different tissues (e.g., macrophages, keratinocytes, osteoblasts, and intestinal epithelium); however, it is unclear what physiological conditions or stimuli induce interleukin-18 production. To determine physiological conditions for the production of interleukin-18, we have examined the effect of mannitol-induced hyperosmotic conditions on normal human umbilical vein endothelial cells (HUVEC) and eight established human epithelial-like cell lines (Intestine 407, Caco-2, A253, HeLa, SCC25, HT1197, ACHN, A549). Hyperosmotic conditions induced interleukin-18 immunoreactivity in all the human cell lines tested, as detected by immunocytochemistry. The enhanced interleukin-18 production was also observed when mannitol was replaced with NaCl as the inducer of hyperosmotic stress. Enzyme-linked immunosorbent assays revealed that interleukin-18 concentrations in cell extracts were significantly increased by hyperosmotic conditions. Reporter gene assays also revealed that hyperosmotic conditions stimulated transcriptional activity of the interleukin-18 promoter. These results show for the first time that hyperosmotic stress is a stimulator of interleukin-18 production in epithelial-like cells.
Takeuchi
M
M
Fujisaki Institute, Hayashibara Biochemical Laboratories, 675-1, Fujisaki, Okayama 702-8006, Japan. fujisaki@hayashibara.co.jp
Okura
T
T
Mori
T
T
Akita
K
K
Ohta
T
T
Ikeda
M
M
Ikegami
H
H
Kurimoto
M
M
D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000096:biosynthesis*; D009997:Osmotic Pressure; D012965:Sodium Chloride
D020382:Interleukin-18; D012965:Sodium Chloride