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Modulation of human enteric epithelial barrier and ion transport function by Peyer's patch lymphocytes
Jie Chen1, Lai-Ling Tsang, Lok-Sze Ho
1Department of Physiology, Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Aim:
To investigate the role of Peyer's patch lymphocytes in the regulation of enteric epithelial barrier and ion transport function in homeostasis and host defense.
Methods:
Mouse Peyer's patch lymphocytes were co-cultured with human intestinal epithelial cell line Caco-2 either in the mixed or separated (isolated but permeable compartments) culture configuration. Barrier and transport functions of the Caco-2 epithelial monolayers were measured with short-circuit current (Isc) technique. Release of cytokines was measured by enzyme-linked immunosorbent assay (ELISA) and cytokine mRNA expression was analyzed by semi-quantitative RT-PCR. Barrier and iontransport functions of both culture conditions following exposure to Shigella lipopolysaccharide (LPS) were also examined.
Results:
The transepithelial resistance (TER) of the epithelial monolayers co-cultured with Peyer's patch lymphocytes was maintained whereas that of the Caco-2 monolayers alone significantly decreased after eight days in culture. The forskolin-induced anion secretion, in either absence or presence of LPS, was significantly suppressed in the both co-cultures as compared with the Caco-2 cells alone. Furthermore, only the mixed co-culture condition induced the expression and release of mIL-6 from Peyer's patch lymphocytes, which could be further enhanced by LPS. However, both co-culture conditions suppressed expression and release of epithelial hIL-8 under the unstimulated conditions, while the treatment with LPS stimulated their hIL-8 expression and release.
Conclusion:
Peyer's patch lymphocytes may modulate intestinal epithelial barrier and ion transport function in homeostasis and host defense via cell-cell contact and cytokine signaling.