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Analysis of an IL-10 polymorphism in idiopathic pulmonary fibrosis

Genes & Immunity volume 4, pages 258–264 (2003)Cite this article

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic disorder of the lung parenchyma. We have demonstrated changes in IL-10 protein production by alveolar macrophages (AMs) from patients with IPF, which we hypothesise could be because of an IL-10 gene polymorphism. We have screened the coding sequence and 3′ untranslated region of IL-10 for polymorphisms using single-standard conformational polymorphism analysis. A novel polymorphism was identified resulting in a G to A substitution of +43 nucleotides from the start codon changing glycine to arginine at amino acid 15 of the signal peptide sequence. We have introduced the signal peptide mutation into the IL-10 gene and compared secretion of the mutant and wild-type forms after transient transfection of COS-7 cells. Our studies showed that the signal peptide mutation did not have a significant effect on secretion at 24 h post-transfection (P=0.4529 by Mann-Whitney test). However, by 48 h there are significantly lower levels of mutant IL-10 (P=0.0515). There were no differences in the level of cell-associated IL-10 at either 24 or 48 h (P=0.9296 and 0.4268). We suggest that the mutation could affect the efficiency of protein translocation and signal peptide cleavage resulting in lower levels of IL-10 protein secretion.

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Author notes

  1. H A Whittington: Supported by the British Lung Foundation.

Authors and Affiliations

  1. Lung Research Group, University of Bristol Medical School Unit, Southmead Hospital, Westbury on Trym, Bristol, UK

    H A Whittington, R W Freeburn, S I H Godinho & A B Millar

  2. North West Lung Research Centre, Wythenshawe Hospital, Manchester, UK

    J Egan & Y Haider

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  1. H A Whittington
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  2. R W Freeburn
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  3. S I H Godinho
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  4. J Egan
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  5. Y Haider
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  6. A B Millar
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Correspondence to A B Millar.

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Whittington, H., Freeburn, R., Godinho, S. et al. Analysis of an IL-10 polymorphism in idiopathic pulmonary fibrosis. Genes Immun 4, 258–264 (2003). https://doi.org/10.1038/sj.gene.6363959

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