Diltiazem inhibits transferrin receptor expression and causes G1 arrest in normal and neoplastic T cells

Transferrin receptor expression is essential for the proliferation of both normal and malignant T cells. While transferrin receptor expression in normal T cells is tightly coupled to interleukin-2 receptor expression, transferrin receptor expression in malignant cells is usually constitutive and is released from this constraint. Temporally, the appearance of these membrane receptors is preceded by changes in the expression of the proto-oncogenes c-myc and c-myb. In addition, although an increase in the level of intracellular free calcium occurs early in the sequence of T-cell activation, the activation events dependent on this calcium flux have not been resolved. In the present study we report that diltiazem, an ion channel-blocking agent that inhibits calcium influx, arrested the growth in vitro of both normal and malignant human T cells in the G1 phase of the cell cycle. However, diltiazem did not inhibit the expression of c-myc or interleukin-2 receptor mRNA and protein in normal mitogen-activated T cells or the constitutive expression of c-myc and c-myb mRNA in malignant T cells (T acute lymphoblastic leukemia cells). In contrast, diltiazem prevented the induction of transferrin receptor (mRNA and protein) in normal T cells and caused a progressive loss of transferrin receptor (mRNA and protein) in malignant T cells. These data demonstrate that diltiazem can dissociate several growth-related processes normally occurring in G1 and thereby disrupt the biochemical cascade leading to cell proliferation.

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Diltiazem inhibits transferrin receptor expression and causes G1 arrest in normal and neoplastic T cells.

Molecular and Cellular Biology ◽

10.1128/mcb.6.12.4244 ◽

1986 ◽

Vol 6 (12) ◽

pp. 4244-4250 ◽

Cited By ~ 14

Author(s):

L M Neckers ◽

S Bauer ◽

R C McGlennen ◽

J B Trepel ◽

K Rao ◽

...

Keyword(s):

T Cells ◽

Transferrin Receptor ◽

Interleukin 2 ◽

Receptor Expression ◽

Calcium Flux ◽

G1 Arrest ◽

Receptor Mrna ◽

Interleukin 2 Receptor ◽

Transferrin Receptor Expression ◽

Malignant T Cells

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An Upregulation of Interleukin-2 Receptor, Transferrin Receptor Expression and Cytokine Production Mediated by Hemin in Human Peripheral Blood Mononuclear CelIs

International Journal of Urology ◽

10.1111/j.1442-2042.1996.tb00515.x ◽

1996 ◽

Vol 3 (3) ◽

pp. 191-195

Author(s):

Akira Tsuji ◽

Nariyoshi Shinomiya ◽

Masamichi Hayakawa ◽

Hiroshi Nakamura

Keyword(s):

Peripheral Blood ◽

Transferrin Receptor ◽

Cytokine Production ◽

Human Peripheral Blood ◽

Interleukin 2 ◽

Receptor Expression ◽

Peripheral Blood Mononuclear ◽

Interleukin 2 Receptor ◽

Transferrin Receptor Expression

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INHIBITION OF INTERLEUKIN 2 RECEPTOR EXPRESSION IN NORMAL HUMAN T CELLS BY CYCLOSPORINE

Transplantation Journal ◽

10.1097/00007890-199201000-00030 ◽

1992 ◽

Vol 53 (1) ◽

pp. 146-150 ◽

Cited By ~ 13

Author(s):

BAOGUI LI ◽

PRABODH K. SEHAJPAL ◽

AJIT SUBRAMANIAM ◽

ANTONIO JOSEPH ◽

KURT H. STENZEL ◽

...

Keyword(s):

T Cells ◽

Interleukin 2 ◽

Receptor Expression ◽

Interleukin 2 Receptor ◽

Human T Cells ◽

Normal Human

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Unsaturated fatty acids suppress interleukin-2 production and transferrin receptor expression by concanavalin A-stimulated rat Iymphocytes

Mediators of Inflammation ◽

10.1155/s0962935192000188 ◽

1992 ◽

Vol 1 (2) ◽

pp. 107-112 ◽

Cited By ~ 45

Author(s):

Philip C. Calder ◽

Eric A. Newsholme

Keyword(s):

Fatty Acids ◽

Transferrin Receptor ◽

Lymphocyte Proliferation ◽

Culture Medium ◽

Unsaturated Fatty Acids ◽

Saturated Fatty Acids ◽

Interleukin 2 ◽

Receptor Expression ◽

T Lymphocyte Proliferation ◽

Transferrin Receptor Expression

The proliferation of T-lymphocytes is dependent upon their ability to synthesize and secrete the cytokine, interleukin-2, and to express cell surface receptors for interleukin-2 and transferrin. We have previously reported that certain fatty acids inhibit mitogen-stimulated T-lymphocyte proliferation. We now report that unsaturated fatty acids decrease the concentration of interleukin-2 in the culture medium of such cells by up to 45%. This suggests that unsaturated fatty acids inhibit lymphocyte proliferation by suppressing interleukin-2 production. However, lymphocyte proliferation was only partially restored by addition of exogenous interleukin-2 to cell culture medium in the presence of unsaturated fatty acids, indicating that these fatty acids also affect other processes involved in the control of proliferation. Saturated fatty acids, which also inhibit lymphocyte proliferation, did not affect the interleukin-2 concentration in the culture medium suggesting a different mechanism for their action. Neither saturated nor unsaturated fatty acids affected the expression of the interleukin-2 receptor by mitogenstimulated lymphocytes. In contrast, unsaturated fatty acids decreased expression of the transferrin receptor by up to 50%. These observations suggest that the mechanism by which unsaturated fatty acids inhibit lymphocyte proliferation involves suppression of interleukin-2 production and of transferrin receptor expression. The mechanism for the inhibitory action of saturated fatty acids is not clear.

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Activated interstitial and intraepithelial thyroid lymphocytes in autoimmune thyroid disease

Acta Endocrinologica ◽

10.1530/acta.0.1190161 ◽

1988 ◽

Vol 119 (2) ◽

pp. 161-166 ◽

Cited By ~ 9

Author(s):

Shara B. Cohen ◽

Anthony P. Weetman

Keyword(s):

T Cells ◽

Autoimmune Thyroiditis ◽

Transferrin Receptor ◽

Autoimmune Thyroid Disease ◽

Receptor Expression ◽

Graves Disease ◽

Follicular Cells ◽

Autoimmune Thyroid ◽

Thyroid Follicular Cells ◽

Transferrin Receptor Expression

Abstract. This study has further characterised the thyroid lymphocytic infiltrate in Graves' disease and Hashimoto's thyroiditis. Two population of lymphocytes were identified. The interstitial population occurred as a diffuse and a focal infiltrate; most cells were CD3-positive (T cells) and in 4 of 6 glands CD8 (suppressor-cytotoxic)-positive T cells predominated. The intraepithelial population was CD3-negative, CD8-positive. Both populations also contained a few NK (Leu 11b positive cells) in some glands. Many of the lymphocytes in both populations stained with UCHL1 and RFT2 suggesting that these are primed and activated cells, borne out by staining for transferrin receptor expression. Although thyroid follicular cells were Ia-positive, macrophages and dentritic cells were found in all cases, so that a role for antigen-presentation by all three potential candidates in autoimmune thyroiditis is possible.

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