Cloning and mutation analysis of the human IL-18 promoter: a possible roleof polymorphisms in expression regulation

Citation
V. Giedraitis et al., Cloning and mutation analysis of the human IL-18 promoter: a possible roleof polymorphisms in expression regulation, J NEUROIMM, 112(1-2), 2001, pp. 146-152
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROIMMUNOLOGY
ISSN journal
0165-5728 → ACNP
Volume
112
Issue
1-2
Year of publication
2001
Pages
146 - 152
Database
ISI
SICI code
0165-5728(20010101)112:1-2<146:CAMAOT>2.0.ZU;2-B
Abstract
Interleukin-18 is a proinflammatory cytokine, which strongly induces IFN-ga mma production. We have cloned the human IL-18 promoter and screened for po ssible polymorphisms. Three single nucleotide polymorphisms were detected i n the promoter and two polymorphisms in the 5'-nontranslated region of the gene. Three combinations of these polymorphisms were observed in the Swedis h population. All IL-18 promoter alleles were found to have clear promoter activity when inserted into a luciferase reporter vector. There were no sig nificant differences in promoter activity between alleles without stimulati on, but after stimulation with PMA/ionomicin one of the alleles had clearly lower activity than the other (P<0.01). Measurement of IL-18 and IFN-<gamm a> production in 48 multiple sclerosis patients by RT-PCR showed slightly h igher expression of IL-18 in individuals homozygous for the most frequent h aplotype. Two IL-18 promoter polymorphisms were analyzed by sequence specif ic PCR in 208 multiple sclerosis patients and 139 healthy controls, however , no significant differences were found. In summary, our data indicate that common IL-18 promoter polymorphisms influence the expression of IL-18 and potentially also of IFN-gamma. (C) 2001 Elsevier Science B.V. All rights re served.