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PMID: 1940795 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of cytokine production in the human thymus: epidermal growth factor and transforming growth factor alpha regulate mRNA levels of interleukin 1 alpha (IL-1 alpha), IL-1 beta, and IL-6 in human thymic epithelial cells at a post-transcriptional level.

The Journal of experimental medicine ·Vol. 174 ·No. 5 ·1991-11-01 ·Pages 1147-57

Le PT, Lazorick S, Whichard LP, Haynes BF, Singer KH

Abstract

Human thymic epithelial (TE) cells produce interleukin 1 alpha (IL-1 alpha), IL-1 beta, and IL-6, cytokines that are important for thymocyte proliferation. The mRNAs for these cytokines are short-lived and are inducible by multiple stimuli. Thus, the steady-state levels for IL-1 and IL-6 mRNAs are critical in establishing the final cytokine protein levels. In this study we have evaluated the effect of epidermal growth factor (EGF), a growth factor for TE cells, and its homologue transforming growth factor alpha (TGF-alpha), on primary cultures of normal human TE cells for the levels of IL-1 alpha, IL-1 beta, IL-6, and TGF-alpha mRNA. We showed that TE cells expressed EGF receptors (EGF-R) in vitro and in vivo, and that treatment of TE cells with EGF or TGF-alpha increased IL-1 and IL-6 biological activity and mRNA levels for IL-1 alpha, IL-1 beta, and IL-6. Neither EGF nor TGF-alpha increased transcription rates of IL-1 alpha, IL-1 beta, and IL-6 genes, but rather both EGF and TGF-alpha increased cytokine mRNA stability. By indirect immunofluorescence assay, TGF-alpha was localized in medullary TE cells and thymic Hassall's bodies while EGF-R was localized to TE cells throughout the thymus. Thus, TGF-alpha and EGF are critical regulatory molecules for production of TE cell-derived cytokines within the thymus and may function as key modulators of human T cell development in vivo.

MeSH Terms
Cells, Cultured Cycloheximide/pharmacology Dactinomycin/pharmacology Epidermal Growth Factor/pharmacology Epithelium/metabolism ErbB Receptors/analysis Humans Interleukin-1/biosynthesis,genetics Interleukin-6/biosynthesis,genetics RNA, Messenger/analysis Thymus Gland/metabolism Transcription, Genetic Transforming Growth Factor alpha/pharmacology
Chemicals
Interleukin-1 Interleukin-6 RNA, Messenger Transforming Growth Factor alpha Dactinomycin Epidermal Growth Factor Cycloheximide ErbB Receptors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Le P T
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Lazorick S
Whichard L P
Haynes B F
Singer K H
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.174.5.1147
Published
1991-11-01
Pages
1147-57
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118979
Subset
IM
Grants
NIAMS NIH HHS · AR-34808 · United States
NIAMS NIH HHS · AR-39162 · United States
NCI NIH HHS · CA-28936 · United States
External Links
PubMed source DOI: 10.1084/jem.174.5.1147 PMC Full Text View journal details
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