Induction of endothelin-1 synthesis by IL-2 and its modulation of rat intestinal epithelial cell growth

Takeharu Shigematsu, Soichiro Miura, Masahiko Hirokawa, Ryota Hokari, Hajime Higuchi, Naoyuki Watanabe, Yoshikazu Tsuzuki, Hiroyuki Kimura, Shinichiro Tada, Ruri C. Nakatsumi, Hidetsugu Saito, Hiromasa Ishii

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18 Citations (Scopus)

Abstract

Endothelin (ET), a vasoconstrictive peptide, is known to have a variety of biological actions. Although ET is released by vascular endothelial cells, other cell populations also have been reported to synthesize and release ET. In this study, we examined whether ET is synthesized by intestinal epithelial cells and whether it affects induction of epithelial cell proliferation by interleukin-2 (IL-2). Subconfluent monolayers of intestinal epithelial cells (IEC-6 and IEC-18) were maintained in serum-free medium before addition of rat IL-2. Both IEC-6 and IEC-18 cells released ET-1 into the medium under unstimulated conditions, as determined by a sandwich ELISA. IL-2 significantly enhanced ET-1 release in a time-dependent manner. ET-3 was not detectable in the culture media of either cell line. Expression of ET-1 and ET-3 mRNA in epithelial cells was assessed by competitive PCR. Both cell lines were shown to express ET-1 mRNA, but no ET-3 mRNA was detected. IL-2 treatment enhanced ET-1 mRNA expression by both IEC-6 and IEC-18 cells. Both cell lines also expressed mRNA for ET(A) and ET(B) receptor subtypes. When cell proliferation was assessed, exogenous ET-1 induced a slight proliferative response in both types of cells that was consistent and significant at low Et-1 concentrations; cell growth was inhibited at a higher concentration (10-7 M). IL-2 produced a significant proliferative response in both cell lines. However, the addition of ET-1 (10-7 M) to culture media attenuated the IL-2-induced increase in cell proliferation. ET(A)-receptor antagonists significantly enhanced cellular proliferation, suggesting involvement of the ET(A) receptor in modulation of IL-2-induced intestinal epithelial cell growth.

Original languageEnglish
Pages (from-to)G556-G563
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume275
Issue number3 38-3
DOIs
Publication statusPublished - 1998 Sep

Keywords

  • ET(A) receptor
  • mRNA expression

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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    Shigematsu, T., Miura, S., Hirokawa, M., Hokari, R., Higuchi, H., Watanabe, N., Tsuzuki, Y., Kimura, H., Tada, S., Nakatsumi, R. C., Saito, H., & Ishii, H. (1998). Induction of endothelin-1 synthesis by IL-2 and its modulation of rat intestinal epithelial cell growth. American Journal of Physiology - Gastrointestinal and Liver Physiology, 275(3 38-3), G556-G563. https://doi.org/10.1152/ajpgi.1998.275.3.g556