The stability of mRNA encoding IL-4 is increased in pulmonary tuberculosis, while stability of mRNA encoding the antagonistic splice variant, IL-4delta2, is not.
The prototype Th2 cytokine IL-4, and its competitive antagonist IL-4delta2, may be important determinants of outcome in human tuberculosis (TB). However, there are no data on how gene expression of these cytokines is regulated. To evaluate this the stability of IL-4 and IL-4delta2 mRNA after the addition of actinomycin-D, was evaluated in whole blood from subjects with pulmonary TB and uninfected healthy volunteers. The Th2/Th1 (IL-4/IFN-gamma) mRNA ratio in unstimulated cells in whole blood was significantly greater in TB subjects than in controls (p<0.05). The mRNA half-life of the agonist (IL-4), but not the antagonist (IL-4delta2), was significantly prolonged in subjects with TB compared to healthy volunteers ( approximately 5-fold, p=0.0016), and the IL-4/IL-4delta2 ratio was higher in TB patients compared to controls (p<0.05). The differential stability of the Th2 agonist, IL-4, compared to the antagonist IL-4delta2, represents a hitherto undescribed post-transcriptional regulatory mechanism that may modulate the polarisation of Th1/Th2 responses in human TB.
Dheda
Keertan
K
Centre for Infectious Diseases and International Health, Royal Free and University College Medical School, London, UK. k.dheda@ucl.ac.uk <k.dheda@ucl.ac.uk>
Chang
Jung-Su
JS
Huggett
Jim F
JF
Kim
Louise U
LU
Johnson
Margaret A
MA
Zumla
Alimuddin
A
Rook
Graham A W
GA
D000328:Adult; D043171:Chromosomal Instability; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D020033:Protein Isoforms; D018418:Th2 Cells / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000235:genetics*
D020033:Protein Isoforms; D015847:Interleukin-4