NDLI: Contribution of single nucleotide polymorphisms of the IL1A gene to the cleavage of precursor IL-1α and its transcription activity

Content Provider	Springer Nature Link
Author	Kawaguchi, Yasushi Tochimoto, Akiko Hara, Masako Kawamoto, Manabu Sugiura, Tomoko Saito, Seiji Kamatani, Naoyuki
Copyright Year	2007
Abstract	We previously demonstrated the association of IL1A gene single nucleotide polymorphisms (SNPs) with susceptibility to systemic sclerosis (SSc) patients. In this study, we explored the effects of SNP on the transcriptional activity and processing of the precursor IL-1α (pre-IL-1α) in skin fibroblasts. Two kinds of promoter regions of the IL1A gene were prepared including C or T at −889, referred to C/IL1A and T/IL1A, and inserted into a luciferase reporter vector (pGL3). Skin fibroblasts were explanted from two SSc patients whose genomic DNA contained GG and TT genotypes at +4845 of the IL1A gene, respectively. Cell lysates were collected and reacted with various concentrations of calpain, and then the processing of pre-IL-1α was analyzed by Western blotting using monoclonal anti-IL-1α antibody. A SNP was determined by the allelic discrimination method using fluorescence-labeled Taq-Man probes. Significant differences in the luciferase activities were not detected between pGL3 (C/IL1A) and pGL3 (T/IL1A) in SSc fibroblasts. Calpain required a 100-fold higher concentration to process the pre-IL-1α containing Ala at the 114th amino acid than that to do containing Ser. The frequency of the GG genotype was significantly higher in SSc patients than that in healthy donors, whereas the frequency of TT genotype was significantly higher in RA patients than that in healthy donors. Our observation showed that the SNP at +4845 affected the enzymatic efficiency of the protease in cleaving pre-IL-1α. Pre-IL-1α with Ala, which was high in frequency in SSc patients, was more resistant to be cleaved by proteases in human sera than pro-IL-1α with Ser.
Starting Page	441
Ending Page	448
Page Count	8
File Format	PDF
ISSN	00937711
Journal	Immunogenetics
Volume Number	59
Issue Number	6
e-ISSN	14321211
Language	English
Publisher	Springer-Verlag
Publisher Date	2007-04-18
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Interleukin-1α Single nucleotide polymorphism Systemic sclerosis Cell Biology Allergology Immunology
Content Type	Text
Resource Type	Article
Subject	Genetics Immunology

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