Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility.
Interleukin-8 (IL-8) has been implicated in the pathogenesis of RSV-induced bronchiolitis. Previously, we have described an association between bronchiolitis disease severity and a specific IL-8 haplotype comprising six single-nucleotide polymorphisms (SNPs) (-251A/+396G/+781T/+1238delA/+1633T/+2767...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2004
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| _version_ | 1797105945688408064 |
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| author | Hacking, D Knight, J Rockett, K Brown, H Frampton, J Kwiatkowski, D Hull, J Udalova, I |
| author_facet | Hacking, D Knight, J Rockett, K Brown, H Frampton, J Kwiatkowski, D Hull, J Udalova, I |
| author_sort | Hacking, D |
| collection | OXFORD |
| description | Interleukin-8 (IL-8) has been implicated in the pathogenesis of RSV-induced bronchiolitis. Previously, we have described an association between bronchiolitis disease severity and a specific IL-8 haplotype comprising six single-nucleotide polymorphisms (SNPs) (-251A/+396G/+781T/+1238delA/+1633T/+2767T, haplotype 2). Here we investigated the functional basis for this association by measuring haplotype-specific transcription in vivo in human primary cells. We found a significant increase in transcript level derived from the IL-8 haplotype 2 relative to the mirror haplotype 1 (-251T/+396T/+781C/+1238insA/+1633C/+2767A) in respiratory epithelial cells but not in lymphocytes. A promoter polymorphism, -251A, present on the high producer haplotype, had no significant affect on the allele-specific level of transcription when analyzed in reporter gene experiments in human respiratory epithelial A549 cells. We proceeded to systematically screen for allele-specific protein-DNA binding in this functional haplotype, which revealed significant differential binding at the +781T/C polymorphism. C/EBP beta was identified as being part of a transcription factor binding complex that preferentially bound in the presence of the +781 T allele. These results suggest that the mechanism for disease susceptibility to RSV-induced bronchiolitis may occur through a haplotype-specific increase in IL-8 transcription, which may be mediated by functional polymorphisms within that haplotype. |
| first_indexed | 2024-03-07T06:54:38Z |
| format | Journal article |
| id | oxford-uuid:fdb66a1a-b14b-44e1-9bbf-869181326062 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:54:38Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:fdb66a1a-b14b-44e1-9bbf-8691813260622022-03-27T13:30:56ZIncreased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fdb66a1a-b14b-44e1-9bbf-869181326062EnglishSymplectic Elements at Oxford2004Hacking, DKnight, JRockett, KBrown, HFrampton, JKwiatkowski, DHull, JUdalova, IInterleukin-8 (IL-8) has been implicated in the pathogenesis of RSV-induced bronchiolitis. Previously, we have described an association between bronchiolitis disease severity and a specific IL-8 haplotype comprising six single-nucleotide polymorphisms (SNPs) (-251A/+396G/+781T/+1238delA/+1633T/+2767T, haplotype 2). Here we investigated the functional basis for this association by measuring haplotype-specific transcription in vivo in human primary cells. We found a significant increase in transcript level derived from the IL-8 haplotype 2 relative to the mirror haplotype 1 (-251T/+396T/+781C/+1238insA/+1633C/+2767A) in respiratory epithelial cells but not in lymphocytes. A promoter polymorphism, -251A, present on the high producer haplotype, had no significant affect on the allele-specific level of transcription when analyzed in reporter gene experiments in human respiratory epithelial A549 cells. We proceeded to systematically screen for allele-specific protein-DNA binding in this functional haplotype, which revealed significant differential binding at the +781T/C polymorphism. C/EBP beta was identified as being part of a transcription factor binding complex that preferentially bound in the presence of the +781 T allele. These results suggest that the mechanism for disease susceptibility to RSV-induced bronchiolitis may occur through a haplotype-specific increase in IL-8 transcription, which may be mediated by functional polymorphisms within that haplotype. |
| spellingShingle | Hacking, D Knight, J Rockett, K Brown, H Frampton, J Kwiatkowski, D Hull, J Udalova, I Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility. |
| title | Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility. |
| title_full | Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility. |
| title_fullStr | Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility. |
| title_full_unstemmed | Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility. |
| title_short | Increased in vivo transcription of an IL-8 haplotype associated with respiratory syncytial virus disease-susceptibility. |
| title_sort | increased in vivo transcription of an il 8 haplotype associated with respiratory syncytial virus disease susceptibility |
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