Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1995 Aug 29;92(18):8353–8357. doi: 10.1073/pnas.92.18.8353

Human intestinal epithelial cells express functional cytokine receptors sharing the common gamma c chain of the interleukin 2 receptor.

H C Reinecker 1, D K Podolsky 1
PMCID: PMC41155  PMID: 7667294

Abstract

Interleukin (IL) 2 signaling requires the dimerization of the IL-2 receptor beta (IL-2R beta) and common gamma (gamma c) chains. The gamma is also a component of the receptors for IL-4, IL-7, and IL-9. To assess the extent and role of the receptor signal transducing system utilizing the gamma c chain on human intestinal epithelial cells, the expression of gamma c, IL-2R beta, and receptor chains specific for IL-4, IL-7, and IL-9 was assessed by reverse transcription-coupled PCR on human intestinal epithelial cell lines and on isolated primary human intestinal epithelial cells. Caco-2, HT-29, and T-84 cells were found to express transcripts for the gamma c and IL-4R chains constitutively. IL-2R beta chain expression was demonstrated in Caco-2 and HT-29 but not in T-84 cells. None of the cell lines expressed mRNA for the IL-2R alpha chain. After stimulation with epidermal growth factor for 24 h Caco-2, HT-29, and T-84 cells expressed transcripts for IL-7R. In addition, Caco-2 and HT-29 cells expressed mRNA for the IL-9R. Receptors for IL-2, IL-4, IL-7, and IL-9 on intestinal epithelial cells lines appeared to be functional; stimulation with these cytokines caused rapid tyrosine phosphorylation of proteins. The relevance of the observations in intestinal epithelial cell lines for intestinal epithelial function in vivo was supported by the demonstration of transcripts for gamma c, IL-2R beta, IL-4R, IL-7R, and IL-9R in primary human intestinal epithelial cells.

Full text

PDF
8354

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Appasamy P. M. Interleukin-7: biology and potential clinical applications. Cancer Invest. 1993;11(4):487–499. doi: 10.3109/07357909309018880. [DOI] [PubMed] [Google Scholar]
  2. Asao H., Kumaki S., Takeshita T., Nakamura M., Sugamura K. IL-2-dependent in vivo and in vitro tyrosine phosphorylation of IL-2 receptor gamma chain. FEBS Lett. 1992 Jun 15;304(2-3):141–145. doi: 10.1016/0014-5793(92)80605-g. [DOI] [PubMed] [Google Scholar]
  3. Chang M. S., Engel G., Benedict C., Basu R., McNinch J. Isolation and characterization of the human interleukin-9 receptor gene. Blood. 1994 Jun 1;83(11):3199–3205. [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Ciacci C., Mahida Y. R., Dignass A., Koizumi M., Podolsky D. K. Functional interleukin-2 receptors on intestinal epithelial cells. J Clin Invest. 1993 Jul;92(1):527–532. doi: 10.1172/JCI116598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colgan S. P., Resnick M. B., Parkos C. A., Delp-Archer C., McGuirk D., Bacarra A. E., Weller P. F., Madara J. L. IL-4 directly modulates function of a model human intestinal epithelium. J Immunol. 1994 Sep 1;153(5):2122–2129. [PubMed] [Google Scholar]
  7. Harrison D. D., Webster H. L. The preparation of isolated intestinal crypt cells. Exp Cell Res. 1969 May;55(2):257–260. doi: 10.1016/0014-4827(69)90489-3. [DOI] [PubMed] [Google Scholar]
  8. Hatakeyama M., Kono T., Kobayashi N., Kawahara A., Levin S. D., Perlmutter R. M., Taniguchi T. Interaction of the IL-2 receptor with the src-family kinase p56lck: identification of novel intermolecular association. Science. 1991 Jun 14;252(5012):1523–1528. doi: 10.1126/science.2047859. [DOI] [PubMed] [Google Scholar]
  9. Izuhara K., Harada N. Interleukin-4 (IL-4) induces protein tyrosine phosphorylation of the IL-4 receptor and association of phosphatidylinositol 3-kinase to the IL-4 receptor in a mouse T cell line, HT2. J Biol Chem. 1993 Jun 25;268(18):13097–13102. [PubMed] [Google Scholar]
  10. Kishimoto T., Taga T., Akira S. Cytokine signal transduction. Cell. 1994 Jan 28;76(2):253–262. doi: 10.1016/0092-8674(94)90333-6. [DOI] [PubMed] [Google Scholar]
  11. Kobayashi N., Kono T., Hatakeyama M., Minami Y., Miyazaki T., Perlmutter R. M., Taniguchi T. Functional coupling of the src-family protein tyrosine kinases p59fyn and p53/56lyn with the interleukin 2 receptor: implications for redundancy and pleiotropism in cytokine signal transduction. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4201–4205. doi: 10.1073/pnas.90.9.4201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kondo M., Takeshita T., Higuchi M., Nakamura M., Sudo T., Nishikawa S., Sugamura K. Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes. Science. 1994 Mar 11;263(5152):1453–1454. doi: 10.1126/science.8128231. [DOI] [PubMed] [Google Scholar]
  13. Kumaki S., Asao H., Takeshita T., Kurahayashi Y., Nakamura M., Beckers T., Engels J. W., Sugamura K. Cell type-specific tyrosine phosphorylation of IL-2 receptor beta chain in response to IL-2. FEBS Lett. 1992 Sep 21;310(1):22–26. doi: 10.1016/0014-5793(92)81137-b. [DOI] [PubMed] [Google Scholar]
  14. Miyazaki T., Kawahara A., Fujii H., Nakagawa Y., Minami Y., Liu Z. J., Oishi I., Silvennoinen O., Witthuhn B. A., Ihle J. N. Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits. Science. 1994 Nov 11;266(5187):1045–1047. doi: 10.1126/science.7973659. [DOI] [PubMed] [Google Scholar]
  15. Nakamura Y., Russell S. M., Mess S. A., Friedmann M., Erdos M., Francois C., Jacques Y., Adelstein S., Leonard W. J. Heterodimerization of the IL-2 receptor beta- and gamma-chain cytoplasmic domains is required for signalling. Nature. 1994 May 26;369(6478):330–333. doi: 10.1038/369330a0. [DOI] [PubMed] [Google Scholar]
  16. Phillips J. O., Everson M. P., Moldoveanu Z., Lue C., Mestecky J. Synergistic effect of IL-4 and IFN-gamma on the expression of polymeric Ig receptor (secretory component) and IgA binding by human epithelial cells. J Immunol. 1990 Sep 15;145(6):1740–1744. [PubMed] [Google Scholar]
  17. Roifman C. M., Wang G. X., Freedman M., Pan Z. Q. IL-7 receptor mediates tyrosine phosphorylation but does not activate the phosphatidylinositol-phospholipase C-gamma 1 pathway. J Immunol. 1992 Feb 15;148(4):1136–1142. [PubMed] [Google Scholar]
  18. Russell S. M., Johnston J. A., Noguchi M., Kawamura M., Bacon C. M., Friedmann M., Berg M., McVicar D. W., Witthuhn B. A., Silvennoinen O. Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID. Science. 1994 Nov 11;266(5187):1042–1045. doi: 10.1126/science.7973658. [DOI] [PubMed] [Google Scholar]
  19. Russell S. M., Keegan A. D., Harada N., Nakamura Y., Noguchi M., Leland P., Friedmann M. C., Miyajima A., Puri R. K., Paul W. E. Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science. 1993 Dec 17;262(5141):1880–1883. doi: 10.1126/science.8266078. [DOI] [PubMed] [Google Scholar]
  20. Seckinger P., Fougereau M. Activation of src family kinases in human pre-B cells by IL-7. J Immunol. 1994 Jul 1;153(1):97–109. [PubMed] [Google Scholar]
  21. Torigoe T., Saragovi H. U., Reed J. C. Interleukin 2 regulates the activity of the lyn protein-tyrosine kinase in a B-cell line. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2674–2678. doi: 10.1073/pnas.89.7.2674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Voss S. D., Robb R. J., Weil-Hillman G., Hank J. A., Sugamura K., Tsudo M., Sondel P. M. Increased expression of the interleukin 2 (IL-2) receptor beta chain (p70) on CD56+ natural killer cells after in vivo IL-2 therapy: p70 expression does not alone predict the level of intermediate affinity IL-2 binding. J Exp Med. 1990 Oct 1;172(4):1101–1114. doi: 10.1084/jem.172.4.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wang L. M., Keegan A. D., Paul W. E., Heidaran M. A., Gutkind J. S., Pierce J. H. IL-4 activates a distinct signal transduction cascade from IL-3 in factor-dependent myeloid cells. EMBO J. 1992 Dec;11(13):4899–4908. doi: 10.1002/j.1460-2075.1992.tb05596.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES