Prostaglandin E2 differentially modulates IL-5 gene expression in activated humanT lymphocytes depending on the costimulatory signal - 09/09/11
Abstract |
Background: Protein kinase A (PKA) activation is documented to be inhibitory for T helper cell (TH1)-like cytokines (IL-2, IFN-γ), whereas TH2-like cytokines (IL-4, IL-5) are not affected or upregulated. We have recently shown that IL-4 gene expression can be inhibited by PKA activation but depends on the mode of T-cell activation. For IL-5 gene expression, we hypothesized that the mode of T-cell activation also determines the ultimate effect of simultaneous PKA activation.
Objectives: The objective of this study was the examination of IL-5 gene expression in healthy T cells activated with various mitogenic stimuli after simultaneous activation of PKA by dibutyryl-cAMP or prostaglandin E2 (PGE2).
Methods: IL-5 mRNA was measured by semiquantitative reverse transcription–polymerase chain reaction or Northern analysis. IL-5 protein was measured by ELISA. Transcriptional mechanisms involved in IL-5 gene expression were determined by nuclear run-on experiments and electrophoretic mobility shift assays. Posttranscriptional mechanisms were determined by actinomycin D chase studies.
Results: Anti-CD2–, anti-CD3–, and anti-CD3 plus anti-CD28–induced IL-5 mRNA were completely inhibited by dibutyryl cyclic AMP (10−3 mol/L) and PGE2 (10-5 mol/L), whereas concanavalin A-induced IL-5 mRNA was partially reduced. The effect of PGE2 was accomplished at the transcriptional level, probably as the result of inhibition of DNA binding of nuclear factor-κB. Anti-CD3 plus anti-CD28–induced IL-5 protein (504 ± 56 pg/ml) was significantly reduced by PGE2 (122 ± 42 pg/ml, p < 0.001). Addition of cytokines that use the IL-2 receptor γC chain (IL-2, IL-7, IL-15) abrogated the PGE2-induced inhibition of IL-5 protein. In contrast, concanavalin A plus PMA–induced IL-5 protein (75 ± 8 pg/ml) was significantly upregulated by the simultaneous addition of PGE2 (128 ± 17 pg/ml, p < 0.03).
Conclusions: PKA activation differentially modulates IL-5 gene expression and depends on the mode of T-cell activation. (J Allergy Clin Immunol 1998;101:231-40.)
Le texte complet de cet article est disponible en PDF.Keywords : T cells, IL-5, prostaglandin E2, protein kinase A, transcription factors
Abbreviations : AP-1:, CD28RC:, Con A:, db-cAMP, GM-CSF:, mAbs:, NFAT:, NF-κB:, PBS:, PGE2:, PKA:, PMA:, RT-PCR:, SDS:, TH1, TH2, etc.:
Plan
 | From the Divisions of aAllergology, bPulmonology, and cHematology, Department of Internal Medicine, University of Groningen, Groningen. |
| Supported by a research grant from the Nederlands Astma Fonds (Dutch Asthma Foundation; grant No. 92.30). |
 | Reprint requests: Henk F. Kauffman, PhD, Department of Allergology, Clinic for Internal Medicine, State University Hospital, P.O. Box 30001, 9700 RB Groningen, The Netherlands. |
| 1/1/86349 |
Vol 101 - N° 2
P. 231-240 - février 1998 Retour au numéro
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