Early immune response and regulation of IL-2 receptor subunits

Millie Hughes-Fulford, Eiko Sugano, Thomas Schopper, Chai-Fei Li, J. B. Boonyaratanakornkit, Augusto Cogoli

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Affymetrix oligonucleotide arrays were used to monitor expression of 8796 genes and probe sets in activated T-cells; analysis revealed that 217 genes were significantly upregulated within 4 h. Induced genes included transcription factors, cytokines and their receptor genes. Analysis by semi-quantitative RT-PCR confirmed the significant induction of IL-2, IL-2Rγ and IL-2Rα. Forty-eight of the 217 induced genes are known to or predicted to be regulated by a CRE promoter/enhancer. We found that T-cell activation caused a significant increase in CREB phosphorylation furthermore, inhibition of the PKC pathway by GF109203 reduced CREB activation by 50% and inhibition of the PKA pathway caused a total block of CREB phosphorylation and significantly reduced IFNγ, IL-2 and IL-2Rα gene expression by approximately 40% (p<0.001). PKCθ plays a major role in T-cell activation: inhibition of PKC significantly reduced the expression of IFNγ, IL-2 and IL-2Rα. Since PKC blocked activation of CREB, we studied potential cross-talk between the PKC and the PKA/MAPK pathways, PMA-stimulated Jurkat cells were studied with specific signal pathway inhibitors. Extracellular signal-regulated kinase-2 (ERK2) pathway was found to be significantly activated greater than seven-fold within 30 min; however, there was little activation of ERK-1 and no activation of JNK or p38 MAPK. Inhibition of the PKA pathway, but not the PKC pathway, resulted in inhibition of ERK1/2 activation at all time points, inhibition of MEK1 and 2 significantly blocked expression of IL-2 and IL-2Rα. Gene expression of IL-2Rα and IFNγ was dependent on PKA in S49 wt cells but not in kin- mutants. Using gel shift analysis, we found that forskolin activation of T-cells resulted in activation of AP1 sites; this increase in nuclear extract AP1 was significantly blocked by MEK1 inhibitor U0126. Taken together, these results suggest that the PKA in addition to PKC and MAPK pathways plays a role in early T-cell activation and induction of IL-2, IL-2Rα and IFNγ gene expression.

Original languageEnglish (US)
Pages (from-to)1111-1124
Number of pages14
JournalCellular Signalling
Volume17
Issue number9
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Fingerprint

Interleukin-2 Receptors
Interleukin-2
T-Lymphocytes
Gene Expression
Genes
Phosphorylation
Cytokine Receptors
Jurkat Cells
Mitogen-Activated Protein Kinase 1
Electrophoretic Mobility Shift Assay
p38 Mitogen-Activated Protein Kinases
Colforsin
Oligonucleotide Array Sequence Analysis
Signal Transduction
Transcription Factors
Polymerase Chain Reaction

Keywords

  • IL-2 receptor
  • IL-2 receptor subunits
  • Immune response
  • Interleukin-2
  • Protein kinase A
  • T-cell activation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hughes-Fulford, M., Sugano, E., Schopper, T., Li, C-F., Boonyaratanakornkit, J. B., & Cogoli, A. (2005). Early immune response and regulation of IL-2 receptor subunits. Cellular Signalling, 17(9), 1111-1124. https://doi.org/10.1016/j.cellsig.2004.12.016

Early immune response and regulation of IL-2 receptor subunits. / Hughes-Fulford, Millie; Sugano, Eiko; Schopper, Thomas; Li, Chai-Fei; Boonyaratanakornkit, J. B.; Cogoli, Augusto.

In: Cellular Signalling, Vol. 17, No. 9, 01.09.2005, p. 1111-1124.

Research output: Contribution to journalArticle

Hughes-Fulford, M, Sugano, E, Schopper, T, Li, C-F, Boonyaratanakornkit, JB & Cogoli, A 2005, 'Early immune response and regulation of IL-2 receptor subunits', Cellular Signalling, vol. 17, no. 9, pp. 1111-1124. https://doi.org/10.1016/j.cellsig.2004.12.016
Hughes-Fulford M, Sugano E, Schopper T, Li C-F, Boonyaratanakornkit JB, Cogoli A. Early immune response and regulation of IL-2 receptor subunits. Cellular Signalling. 2005 Sep 1;17(9):1111-1124. https://doi.org/10.1016/j.cellsig.2004.12.016
Hughes-Fulford, Millie ; Sugano, Eiko ; Schopper, Thomas ; Li, Chai-Fei ; Boonyaratanakornkit, J. B. ; Cogoli, Augusto. / Early immune response and regulation of IL-2 receptor subunits. In: Cellular Signalling. 2005 ; Vol. 17, No. 9. pp. 1111-1124.
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