The mechanism of action of serum immunosuppressive factor in Crohn's disease: It blocks the growth of mitogen-stimulated lymphocytes in early G1 phase through an inhibition of transferrin receptor expression

Yasushi Iwao, T. Hibi, M. Watanabe, Hiromasa Takaishi, Y. Hosoda, A. Hayashi, M. Ohara, Haruhiko Ogata, S. Aiso, K. Toda, M. Tsuchiya

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Abstract

The presence of serum immunosuppressive factor has recently been reported in patients with Crohn's disease. We investigated the mechanism of action of this immunosuppressive factor in vitro. The factor in serum fraction from patients with Crohn's disease had an inhibitory activity on the proliferation of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from healthy volunteers. The growth of tumor cell lines, however, was not inhibited by the factor. While the factor did not influence the production of interleukin 2 (IL 2) or the expression of IL2 receptor of PHA-stimulated PBMCs, it inhibited the expression of transferrin receptor. The effect of the factor on cell cycle of PHA-stimulated PBMCs was examined by flow cytometry analysis. The factor kept the cells in quiescent G0/G1 phase and decreased the number of cells in S phase. Prostaglandin E2, an immunosuppressive substance, may not participate in the inhibitory action of the factor, since indomethacin did not affect the inhibitory activity of the factor. These results suggest that the immunosuppressive factor in serum from patients with Crohn's disease is unique in the mechanism of inhibitory action and further clarification of this factor might contribute to the development of a new diagnostic assay for Crohn's disease and the elucidation of the pathogenesis of this disease.

Original languageEnglish
Pages (from-to)15-27
Number of pages13
JournalJournal of Clinical and Laboratory Immunology
Volume38
Issue number1
Publication statusPublished - 1992

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Transferrin Receptors
G1 Phase
Mitogens
Crohn Disease
Phytohemagglutinins
Lymphocytes
Blood Cells
Immunosuppressive Agents
Growth
Cell Cycle Resting Phase
Interleukin-2 Receptors
Tumor Cell Line
S Phase
Dinoprostone
Indomethacin
Interleukin-2
Healthy Volunteers
Cell Cycle
Flow Cytometry
Cell Count

Keywords

  • Cell cycle
  • Crohn's disease
  • Immunosuppression
  • Lymphocyte
  • Proliferation

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "The mechanism of action of serum immunosuppressive factor in Crohn's disease: It blocks the growth of mitogen-stimulated lymphocytes in early G1 phase through an inhibition of transferrin receptor expression",
abstract = "The presence of serum immunosuppressive factor has recently been reported in patients with Crohn's disease. We investigated the mechanism of action of this immunosuppressive factor in vitro. The factor in serum fraction from patients with Crohn's disease had an inhibitory activity on the proliferation of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from healthy volunteers. The growth of tumor cell lines, however, was not inhibited by the factor. While the factor did not influence the production of interleukin 2 (IL 2) or the expression of IL2 receptor of PHA-stimulated PBMCs, it inhibited the expression of transferrin receptor. The effect of the factor on cell cycle of PHA-stimulated PBMCs was examined by flow cytometry analysis. The factor kept the cells in quiescent G0/G1 phase and decreased the number of cells in S phase. Prostaglandin E2, an immunosuppressive substance, may not participate in the inhibitory action of the factor, since indomethacin did not affect the inhibitory activity of the factor. These results suggest that the immunosuppressive factor in serum from patients with Crohn's disease is unique in the mechanism of inhibitory action and further clarification of this factor might contribute to the development of a new diagnostic assay for Crohn's disease and the elucidation of the pathogenesis of this disease.",
keywords = "Cell cycle, Crohn's disease, Immunosuppression, Lymphocyte, Proliferation",
author = "Yasushi Iwao and T. Hibi and M. Watanabe and Hiromasa Takaishi and Y. Hosoda and A. Hayashi and M. Ohara and Haruhiko Ogata and S. Aiso and K. Toda and M. Tsuchiya",
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T1 - The mechanism of action of serum immunosuppressive factor in Crohn's disease

T2 - It blocks the growth of mitogen-stimulated lymphocytes in early G1 phase through an inhibition of transferrin receptor expression

AU - Iwao, Yasushi

AU - Hibi, T.

AU - Watanabe, M.

AU - Takaishi, Hiromasa

AU - Hosoda, Y.

AU - Hayashi, A.

AU - Ohara, M.

AU - Ogata, Haruhiko

AU - Aiso, S.

AU - Toda, K.

AU - Tsuchiya, M.

PY - 1992

Y1 - 1992

N2 - The presence of serum immunosuppressive factor has recently been reported in patients with Crohn's disease. We investigated the mechanism of action of this immunosuppressive factor in vitro. The factor in serum fraction from patients with Crohn's disease had an inhibitory activity on the proliferation of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from healthy volunteers. The growth of tumor cell lines, however, was not inhibited by the factor. While the factor did not influence the production of interleukin 2 (IL 2) or the expression of IL2 receptor of PHA-stimulated PBMCs, it inhibited the expression of transferrin receptor. The effect of the factor on cell cycle of PHA-stimulated PBMCs was examined by flow cytometry analysis. The factor kept the cells in quiescent G0/G1 phase and decreased the number of cells in S phase. Prostaglandin E2, an immunosuppressive substance, may not participate in the inhibitory action of the factor, since indomethacin did not affect the inhibitory activity of the factor. These results suggest that the immunosuppressive factor in serum from patients with Crohn's disease is unique in the mechanism of inhibitory action and further clarification of this factor might contribute to the development of a new diagnostic assay for Crohn's disease and the elucidation of the pathogenesis of this disease.

AB - The presence of serum immunosuppressive factor has recently been reported in patients with Crohn's disease. We investigated the mechanism of action of this immunosuppressive factor in vitro. The factor in serum fraction from patients with Crohn's disease had an inhibitory activity on the proliferation of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from healthy volunteers. The growth of tumor cell lines, however, was not inhibited by the factor. While the factor did not influence the production of interleukin 2 (IL 2) or the expression of IL2 receptor of PHA-stimulated PBMCs, it inhibited the expression of transferrin receptor. The effect of the factor on cell cycle of PHA-stimulated PBMCs was examined by flow cytometry analysis. The factor kept the cells in quiescent G0/G1 phase and decreased the number of cells in S phase. Prostaglandin E2, an immunosuppressive substance, may not participate in the inhibitory action of the factor, since indomethacin did not affect the inhibitory activity of the factor. These results suggest that the immunosuppressive factor in serum from patients with Crohn's disease is unique in the mechanism of inhibitory action and further clarification of this factor might contribute to the development of a new diagnostic assay for Crohn's disease and the elucidation of the pathogenesis of this disease.

KW - Cell cycle

KW - Crohn's disease

KW - Immunosuppression

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