Slc11a1 (formerly NRAMP1) gene modulates both acute inflammatory reactions and pristane-induced arthritis in mice

被引:23
作者
Peters, L. C.
Jensen, J. R.
Borrego, A.
Cabrera, W. H. K.
Baker, N.
Starobinas, N.
Ribeiro, O. G.
Ibanez, O. M.
De Franco, M.
机构
[1] Inst Butantan, Immunogenet Lab, BR-05503900 Sao Paulo, Brazil
[2] Inst Adolfo Lutz Registro, Secao Enteroparasitoses, Sao Paulo, Brazil
[3] Trinity Coll Dublin, Dept Biochem, Dublin, Ireland
基金
巴西圣保罗研究基金会;
关键词
pristane-induced arthritis; acute inflammation; Slc11a1; cytokines;
D O I
10.1038/sj.gene.6364358
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Mice selected for the maximum acute inflammatory reaction (AIRmax) are highly susceptible to pristane-induced arthritis ( PIA), whereas mice selected for the minimum response (AIRmin) are resistant. These lines show distinct patterns of leukocyte infiltration and R and S allele frequency disequilibrium of the solute carrier family 11a member 1 (Slc11a1) gene. In order to study the interactions of the Slc11a1 R and S alleles with the inflammation modulating Quantitative Trait Loci (QTL) during PIA development, homozygous AIRmax(RR), AIRmax(SS), AIRmin(RR) and AIRmin(SS) lines were produced by genotype-assisted breedings. These mice received two intraperitoneal injections of 0.5 ml pristane at 60-day intervals, and the subsequent development of arthritis was assessed for 210 days. Cytokine-secreting cell profiles were investigated using enzyme-linked immunospot. Arthritis incidence in AIRmaxRR mice reached 29%, whereas PIA incidence in AIRmaxSS mice was 70% by day 180. AIRmin(RR) mice were resistant, whereas 13.3% of AIRminSS mice became arthritic. The presence of the defective S allele also increased arthritis severity, although acute inflammation was higher in mice bearing the R allele. A predominant Th0/Th2-type response in Slc11a1(SS) mice was observed. These results indicate that Slc11a1 is a strong candidate for the QTL modulating acute inflammation and for PIA.
引用
收藏
页码:51 / 56
页数:6
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