IngentaConnect Transmural pressure induces IL-6 secretion by intestinal epitheli...

Authors: KISHIKAWA, H.¹; MIURA, S.²; YOSHIDA, H.¹; HIROKAWA, M.¹; NAKAMIZO, H.¹; HIGUCHI, H.¹; ADACHI, M.¹; NAKATSUMI, R. C.¹; SUZUKI, H.¹; SAITO, H.¹; ISHII, H.¹

Source: Clinical & Experimental Immunology, Volume 129, Number 1, July 2002 , pp. 86-91(6)

Publisher: Blackwell Publishing

Abstract:

SUMMARY

Although intestinal epithelial cells (IECs) are known as an important source for IL-6, it is not known whether mechanical forces affect IL-6 production. We investigated how transmural pressure modulates IL-6 synthesis and activation of transcription factors in IECs. Pressure was loaded onto IEC-18 cells by introducing compressed helium gas into the cell culture flask for 1-48 h. IL-6 release into the culture media was determined by cell proliferation bioassay using an IL-6-dependent mouse hybridoma cell line (7TD1). Exposure to pressure (80 mmHg) significantly enhanced IL-6 release into the culture media from IEC-18 cells at 12 h. Under control conditions, IL-6 secretion was directed to the basolateral side, but after exposure to pressure IL-6 secretion was increased in both the apical and basolateral sides. A nuclear factor kappa B (NF-κB) decoy reversed completely the pressure-induced increase of IL-6 secretion by IEC-18 cells. Pressure treatment enhanced IL-6 mRNA expression in IECs within 6 h. Pressure loading significantly enhanced the activation of both NF-κB and NF-IL-6 from 1h in the nuclear protein of IEC-18 cells as assessed by the electrophoretic mobility shift assay using FITC-conjugated specific primers. Increased phosphorylation of I-kappa B was also demonstrated in the cytosol of IEC cells within 1h by Western blot analysis. These results suggest a possible role for pressure loading in immune modulation of the intestinal mucosa by the stimulation of IL-6 release from intestinal epithelial cells.

Keywords: intestinal epithelial cells IL-6 NF-κB NF-IL-6 transmural pressure

Document Type: Research article

DOI: 10.1046/j.1365-2249.2002.01895.x

Affiliations: 1: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan, and 2: Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan

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Transmural pressure induces IL-6 secretion by intestinal epithelial cells