Complex effects of IL1A polymorphism and calpain inhibitors on interleukin 1a (IL-1a) mRNA levels and secretion of IL-1a protein
Alleles of IL1A-889(C>T) and IL1A+4845(G>T) are in linkage disequilibrium. Interleukin 1a (IL-1a) is produced as a precursor protein and cleaved at positions 117-118 by calpain, generating a mature protein for export. IL1A+4845 affects amino acids expressed at position 114 and hence ma...
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| Format: | Journal Article |
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Blackwell Munksgaard
2008
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| Online Access: | http://hdl.handle.net/20.500.11937/5236 |
| _version_ | 1848744739870867456 |
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| author | Lee, S. Temple, S. Roberts, S. Price, Patricia |
| author_facet | Lee, S. Temple, S. Roberts, S. Price, Patricia |
| author_sort | Lee, S. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Alleles of IL1A-889(C>T) and IL1A+4845(G>T) are in linkage disequilibrium. Interleukin 1a (IL-1a) is produced as a precursor protein and cleaved at positions 117-118 by calpain, generating a mature protein for export. IL1A+4845 affects amino acids expressed at position 114 and hence may modulate calpain-mediated cleavage. We sought evidence for this mechanism in intact cells. Blood leukocytes from heterozygous donors released more IL-1a protein than cells from IL1A(1,1) donors, while release from IL1A(2,2) cells was variable. Genotype did not affect levels of IL-1a mRNA, so differential cleavage of the precursor is a feasible mechanism. However, genotype also had no effect on inhibition of IL-1a release by pretreatment with calpain inhibitors, and calpain inhibitors reduced IL-1a and tumor necrosis factor a mRNA levels. Hence, calpain inhibitors probably affect inhibition of signal transduction pathway rather than cleavage of IL-1a protein. As ratios of µ-calpain/calpastatin were lowest in heterozygous donors, genetically determined IL-1a levels may modulate transcription of calpain and calpastatin. This could reduce the impact of IL1A genotype on IL-1a secretion and amplify individual variation in levels generated in culture. © 2008 The Authors. |
| first_indexed | 2025-11-14T06:06:15Z |
| format | Journal Article |
| id | curtin-20.500.11937-5236 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:06:15Z |
| publishDate | 2008 |
| publisher | Blackwell Munksgaard |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-52362017-09-13T14:44:36Z Complex effects of IL1A polymorphism and calpain inhibitors on interleukin 1a (IL-1a) mRNA levels and secretion of IL-1a protein Lee, S. Temple, S. Roberts, S. Price, Patricia Alleles of IL1A-889(C>T) and IL1A+4845(G>T) are in linkage disequilibrium. Interleukin 1a (IL-1a) is produced as a precursor protein and cleaved at positions 117-118 by calpain, generating a mature protein for export. IL1A+4845 affects amino acids expressed at position 114 and hence may modulate calpain-mediated cleavage. We sought evidence for this mechanism in intact cells. Blood leukocytes from heterozygous donors released more IL-1a protein than cells from IL1A(1,1) donors, while release from IL1A(2,2) cells was variable. Genotype did not affect levels of IL-1a mRNA, so differential cleavage of the precursor is a feasible mechanism. However, genotype also had no effect on inhibition of IL-1a release by pretreatment with calpain inhibitors, and calpain inhibitors reduced IL-1a and tumor necrosis factor a mRNA levels. Hence, calpain inhibitors probably affect inhibition of signal transduction pathway rather than cleavage of IL-1a protein. As ratios of µ-calpain/calpastatin were lowest in heterozygous donors, genetically determined IL-1a levels may modulate transcription of calpain and calpastatin. This could reduce the impact of IL1A genotype on IL-1a secretion and amplify individual variation in levels generated in culture. © 2008 The Authors. 2008 Journal Article http://hdl.handle.net/20.500.11937/5236 10.1111/j.1399-0039.2008.01052.x Blackwell Munksgaard restricted |
| spellingShingle | Lee, S. Temple, S. Roberts, S. Price, Patricia Complex effects of IL1A polymorphism and calpain inhibitors on interleukin 1a (IL-1a) mRNA levels and secretion of IL-1a protein |
| title | Complex effects of IL1A polymorphism and calpain inhibitors on interleukin 1a (IL-1a) mRNA levels and secretion of IL-1a protein |
| title_full | Complex effects of IL1A polymorphism and calpain inhibitors on interleukin 1a (IL-1a) mRNA levels and secretion of IL-1a protein |
| title_fullStr | Complex effects of IL1A polymorphism and calpain inhibitors on interleukin 1a (IL-1a) mRNA levels and secretion of IL-1a protein |
| title_full_unstemmed | Complex effects of IL1A polymorphism and calpain inhibitors on interleukin 1a (IL-1a) mRNA levels and secretion of IL-1a protein |
| title_short | Complex effects of IL1A polymorphism and calpain inhibitors on interleukin 1a (IL-1a) mRNA levels and secretion of IL-1a protein |
| title_sort | complex effects of il1a polymorphism and calpain inhibitors on interleukin 1a (il-1a) mrna levels and secretion of il-1a protein |
| url | http://hdl.handle.net/20.500.11937/5236 |