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TGF-beta differentially modulates epidermal growth factor-mediated increases in leukemia-inhibitory factor, IL-6, IL-1 alpha, and IL-1 beta in human thymic epithelial cells.
J Immunol. 1997 Mar 15; 158(6):2704-12.JI

Abstract

The regulation of cytokine production by thymic epithelial cells (TEC) in the thymus is under coordinated and temporal control and is important for the development of T cells. Human TEC express TGF-beta R and epidermal growth factor (EGF) receptor, and produce TGF-beta 3 in vitro and in vivo. Furthermore, EGF has been shown to increase IL-1 alpha, IL-1 beta, IL-6 mRNA and protein levels in human TEC. Since EGF has been shown to modulate TGF-beta effector functions, we determined whether TGF-beta can modulate EGF-mediated increases in cytokine gene expression in human TEC. We established that a single TEC expresses both EGF receptor and TGF-beta R. TGF-beta plus EGF synergistically increased leukemia-inhibitory factor (LIF), additively increased IL-6, but had little effect on IL-1 alpha and IL-1 beta mRNA levels. In contrast, TGF-beta alone increased LIF and IL-6, had little effect on IL-1 alpha, and slightly decreased IL-1 beta mRNA levels. The increases in LIF and IL-6 mRNA levels by TGF-beta plus EGF correlate with the increases in LIF and IL-6 concentrations in TEC culture supernatants as detected by ELISA. We also determined the mechanism responsible for the increases in cytokine mRNA levels. TGF-beta plus EGF did not affect transcription of LIF and IL-6 genes; this suggests that the increases in the steady state levels of cytokine mRNA were mediated post-transcriptionally, most likely at the level of mRNA stability. Our data demonstrate that TGF-beta modulates TEC cytokine production. We speculate that TGF-beta produced in situ plays a role in thymocyte development by directly affecting thymocyte differentiation and by indirectly modulating TEC cytokine production.

Authors+Show Affiliations

Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9058804

Citation

Schluns, K S., et al. "TGF-beta Differentially Modulates Epidermal Growth Factor-mediated Increases in Leukemia-inhibitory Factor, IL-6, IL-1 Alpha, and IL-1 Beta in Human Thymic Epithelial Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 158, no. 6, 1997, pp. 2704-12.
Schluns KS, Cook JE, Le PT. TGF-beta differentially modulates epidermal growth factor-mediated increases in leukemia-inhibitory factor, IL-6, IL-1 alpha, and IL-1 beta in human thymic epithelial cells. J Immunol. 1997;158(6):2704-12.
Schluns, K. S., Cook, J. E., & Le, P. T. (1997). TGF-beta differentially modulates epidermal growth factor-mediated increases in leukemia-inhibitory factor, IL-6, IL-1 alpha, and IL-1 beta in human thymic epithelial cells. Journal of Immunology (Baltimore, Md. : 1950), 158(6), 2704-12.
Schluns KS, Cook JE, Le PT. TGF-beta Differentially Modulates Epidermal Growth Factor-mediated Increases in Leukemia-inhibitory Factor, IL-6, IL-1 Alpha, and IL-1 Beta in Human Thymic Epithelial Cells. J Immunol. 1997 Mar 15;158(6):2704-12. PubMed PMID: 9058804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TGF-beta differentially modulates epidermal growth factor-mediated increases in leukemia-inhibitory factor, IL-6, IL-1 alpha, and IL-1 beta in human thymic epithelial cells. AU - Schluns,K S, AU - Cook,J E, AU - Le,P T, PY - 1997/3/15/pubmed PY - 1997/3/15/medline PY - 1997/3/15/entrez SP - 2704 EP - 12 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 158 IS - 6 N2 - The regulation of cytokine production by thymic epithelial cells (TEC) in the thymus is under coordinated and temporal control and is important for the development of T cells. Human TEC express TGF-beta R and epidermal growth factor (EGF) receptor, and produce TGF-beta 3 in vitro and in vivo. Furthermore, EGF has been shown to increase IL-1 alpha, IL-1 beta, IL-6 mRNA and protein levels in human TEC. Since EGF has been shown to modulate TGF-beta effector functions, we determined whether TGF-beta can modulate EGF-mediated increases in cytokine gene expression in human TEC. We established that a single TEC expresses both EGF receptor and TGF-beta R. TGF-beta plus EGF synergistically increased leukemia-inhibitory factor (LIF), additively increased IL-6, but had little effect on IL-1 alpha and IL-1 beta mRNA levels. In contrast, TGF-beta alone increased LIF and IL-6, had little effect on IL-1 alpha, and slightly decreased IL-1 beta mRNA levels. The increases in LIF and IL-6 mRNA levels by TGF-beta plus EGF correlate with the increases in LIF and IL-6 concentrations in TEC culture supernatants as detected by ELISA. We also determined the mechanism responsible for the increases in cytokine mRNA levels. TGF-beta plus EGF did not affect transcription of LIF and IL-6 genes; this suggests that the increases in the steady state levels of cytokine mRNA were mediated post-transcriptionally, most likely at the level of mRNA stability. Our data demonstrate that TGF-beta modulates TEC cytokine production. We speculate that TGF-beta produced in situ plays a role in thymocyte development by directly affecting thymocyte differentiation and by indirectly modulating TEC cytokine production. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9058804/TGF_beta_differentially_modulates_epidermal_growth_factor_mediated_increases_in_leukemia_inhibitory_factor_IL_6_IL_1_alpha_and_IL_1_beta_in_human_thymic_epithelial_cells_ DB - PRIME DP - Unbound Medicine ER -