Abstract
Intestinal epithelial cells interact with immune cells located in the intestinal epithelium via soluble factors, and the disordered cellular communication is known as one of the factors of intestinal inflammation, such as inflammatory bowel diseases (IBD). Recently the number of IBD patients has been increasing probably due to westernization of the food style. But the therapeutic method has not yet been established since the diseases are induced by a lot of complicated factors. An in vitro model using a coculture system of human intestinal epithelial-like Caco-2 cells and macrophage-like THP-1 cells was constructed to analyze the effect of macrophages on intestinal epithelial cells. Coculturing with THP-1 cells induced cell damage to Caco-2 cells, which was caused by TNF-α secreted from THP-1 cells. By morphological and biochemical analysis, the disrupted Caco-2 cell monolayers showed both apoptotic and necrotic characteristics. TNFRI, NF-κB, and ERK seemed to have been involved in this disruption. In this study, we further analyzed this phenomenon to reveal the pathogenic mechanism of the intestinal inflammation. Increased expression of genes related to immunity and apoptosis was observed through a DNA microarray analysis in Caco-2 cells cocultured with THP-1 cells. Among the genes, IEX-1 mRNA expression was most significantly up-regulated, and this up-regulation was likely to be induced, at least partly, by TNF-α. IL-1β secretion from THP-1 cells increased by coculturing, and it also seemed to be involved in IEX-1 mRNA expression. In conclusion, these results suggest that the phenomenon observed in this system is similar in some respects to that observed with intestinal inflammation, and this coculture system could be useful to investigate preventive or therapeutic methods for the intestinal inflammation.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Satsu, H., Ishimoto, Y., Nakano, T., Mochizuki, T., Iwanaga, T., and Shimizu, M. (2006) Induction by activated macrophage-like THP-1 cells of apoptotic and necrotic cell death in intestinal epithelial Caco-2 monolayers via tumor necrosis factor-alpha. Exp. Cell Res. 312: 3909–3919.
Puleston, J., Cooper, M., Murch, S., Bid, K., Makh, S., Ashwood, P., Bingham, A.H., Green, H., Moss, P., Dhillon, A., Morris, R., Strobel, S., Gelinas, R., Pounder, R.E., and Platt, A. (2005) A distinct subset of chemokines dominates the mucosal chemokine response in inflammatory bowel disease. Aliment. Pharmacol. Ther. 21: 109–120.
Andoh, A., Kinoshita, K., Rosenberg, I., and Podolsky, D.K. (2001) Intestinal trefoil factor induces decay-accelerating factor expression and enhances the protective activities against complement activation in intestinal epithelial cells. J. Immunol. 167: 3887–3893.
Berstad, A.E. and Brandtzaeg, P. (1998) Expression of cell membrane complement regulatory glycoproteins along the normal and diseased human gastrointestinal tract. Gut 42: 522–529.
Uesu, T., Mizuno, M., Inoue, H., Tomoda, J., and Tsuji, T. (1995) Enhanced expression of decay accelerating factor and CD59/homologous restriction factor 20 on the colonic epithelium of ulcerative colitis. Lab Invest. 72: 587–591.
Daniels, G. (1989) Cromer-released antigens–blood group determinats on decay-accelerating factor. Vox Sang. 56: 205–211.
Wu, M.X. (2003) Roles of the stress-induced gene IEX-1 in regulation of cell death and oncogenesis. Apoptosis 8: 11–18.
Zhang, Y., Schlossman, S.F., Edwards, R.A., Ou, C.N., Gu, J., Wu, M.X. (2002) Impaired apoptosis, extended duration of immune responses, and a lupus-like autoimmune disease in IEX-1-transgenic mice. Proc. Natl. Acad. Sci. USA 99: 878–883.
Osawa, Y., Nagaki, M., Banno, Y., Brenner, D.A., Nozawa, Y., Moriwaki, H., and Nakashima, S. (2003) Expression of the NF-kappaB target gene X-ray-inducible immediate early response factor-1 short enhances TNF-alpha-induced hepatocyte apoptosis by inhibiting Akt activation. J. Immunol. 170: 4053–4060.
Shen, L., Guo, J., Santos-Berrios, C., and Wu, M.X. (2006) Distinct domains for anti-and pro-apoptotic activities of IEX-1. J. Biol. Chem. 281: 15304–15311.
Sebens Muerkoster, S., Rausch, A.V., Isberner, A., Minkenberg, J., Blaszczuk, E., Witt, M., Folsch, U.R., Schmitz, F., Schafer, H., and Arlt, A. (2008) The apoptosis-inducing effect of gastrin on colorectal cancer cells relates to an increased IEX expression mediating NF-kappaB inhibition. Oncogene 27: 1122–1134.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media B.V.
About this paper
Cite this paper
Ishimoto, Y., Satsu, H., Mochizuki, T., Totsuka, M., Shimizu, M. (2010). In Vitro Analysis of the Interaction Between Human Intestinal Epithelial Cells and Macrophage-Like Cells. In: Kamihira, M., Katakura, Y., Ito, A. (eds) Animal Cell Technology: Basic & Applied Aspects. Animal Cell Technology: Basic & Applied Aspects, vol 16. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3892-0_37
Download citation
DOI: https://doi.org/10.1007/978-90-481-3892-0_37
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-3891-3
Online ISBN: 978-90-481-3892-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)