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J Allergy Clin Immunol. 1999 Nov;104(5):978-82.

Asthmatic airway biopsy specimens are more likely to express the IL-4 alternative splice variant IL-4delta2.

Author information

1
Department of Respiratory Medicine, Alfred Hospital and Monash University Medical School, Melbourne, Victoria, Australia.

Abstract

BACKGROUND:

The human IL4 gene, has been shown to express the alternatively spliced messenger (m)RNA IL-4delta2. IL-4delta2 is missing the entire sequence from exon 2 and has been identified as an IL-4 receptor antagonist.

OBJECTIVE:

We sought to distinguish IL-4 and IL-4delta2 mRNA in respiratory tract tissue for the first time.

METHODS:

A novel competitive PCR assay was established with primers designed on either side of the alternative splice junction of the IL4 gene, allowing the simultaneous quantitation of both IL-4 and IL-4delta2 mRNA from one reaction.

RESULTS:

IL-4 and IL-4delta2 were differentially expressed in 4 nasal polyps. No difference was seen in endobronchial biopsy specimens for IL-4 mRNA expression between control subjects (median, 2.8 x 10(2) copies/microg RNA; range, 0-3.7 x 10(3) copies/microg RNA) and asthmatic subjects (median, 1.4 x 10(2) copies/microg RNA; range, 0-4.7 x 10(2) copies/microg RNA). However, significantly more asthmatic subjects (6 of 9) than control subjects (1 of 7) expressed IL-4delta2 (P =. 036). Expression of IL-4 variants was unaffected by atopic status.

CONCLUSIONS:

Given that IL-4delta2 is an IL-4 receptor antagonist, these results indicate that it is crucial to be able to distinguish IL-4delta2 from IL-4 when assessing IL4 gene expression. Increased expression of IL-4delta2 in stable asthmatic subjects suggests that the balance of IL-4 and IL-4delta2 may modulate asthmatic inflammation.

PMID:
10550742
DOI:
10.1016/s0091-6749(99)70078-3
[Indexed for MEDLINE]

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