Neopterin, inflammation-associated product, prolongs erythropoiesis suppression in aged SAMP1 mice due to senescent stromal-cell impairment

被引:5
作者
Aisaki, Kazuo [1 ]
Tsuboi, Ise [1 ]
Harada, Tomonori [1 ]
Oshima, Hideki [1 ]
Yamashita, Akiko [2 ]
Hirabayashi, Yoko [3 ]
Kanno, Jun [3 ]
Inoue, Tohru [1 ]
Aizawa, Shin [1 ]
机构
[1] Nihon Univ, Sch Med, Dept Funct Morphol, Tokyo 1738610, Japan
[2] Nihon Univ, Sch Med, Div Appl Syst Neurosci, Tokyo 1738610, Japan
[3] Natl Inst Hlth Sci, Ctr Biol Safety & Res, Div Cellular & Mol Toxicol, Tokyo 1588501, Japan
基金
日本学术振兴会;
关键词
aging; erythropoiesis; cytokine; stromal cells; neopterin; inflammation; HEMATOPOIETIC MICROENVIRONMENT; IMMUNE ACTIVATION; B-LYMPHOPOIESIS; INTERLEUKIN-11; ANEMIA; EXPRESSION; DEGRADATION; TRYPTOPHAN; BIOMARKER; RESPONSES;
D O I
10.1258/ebm.2011.011303
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Anemia induced by inflammation is well known to be more serious in the elderly than in non-elderly adults; however, the reason why this is so remains unclear. Neopterin produced by monocytes during inflammation promotes myelopoiesis but suppresses B-lymphopoiesis and erythropoiesis, by activating stromal cells in mice. Here, age-related changes in the erythropoietic response to neopterin were determined using senescence accelerated mice (SAMP1) with senescence stromal-cell impairment. Intravenous injection of neopterin into young mice (8-12 weeks old) resulted in a decrease in erythroid progenitor cell number in the bone marrow (BM), concomitant with an increase in myeloid progenitor cell number over one week. Intravenous injection of neopterin into aged mice (30-36 weeks old) resulted in a prolonged decrease in erythroid progenitor cell number in the BM over three weeks and a limited increase in myeloid progenitor cell number over one day. Neopterin treatment induced a decrease in serum erythropoietin concentrations in young mice but not in aged mice. The gene expression of tumor necrosis factor alpha (TNF-alpha), a negative regulator of erythropoiesis, was up-regulated in the BM of both young and aged mice, and the degree of TNF-alpha up-regulation was the same in both groups. The gene expression of interleukin (IL)-11, a positive regulator of erythropoiesis, was also up-regulated over one day in both young and aged mice. However, IL-11 gene expression remained up-regulated thereafter in young mice, whereas it was rapidly down-regulated in aged mice. These data suggest that prolonged suppression of erythropoiesis in aged mice may be due to a decrease in the production of positive regulators rather than to an increase in the production of negative regulators. Our combined data suggest that age-related impairment of stromal cells induces serious anemia in the elderly during inflammation.
引用
收藏
页码:279 / 286
页数:8
相关论文
共 34 条
[1]  
Aizawa S, 1998, HEMATOL ONCOL, V16, P57, DOI 10.1002/(SICI)1099-1069(199806)16:2<57::AID-HON623>3.0.CO
[2]  
2-#
[3]  
Aizawa S, 1998, PTERIDINES, V9, P13
[4]   Anemia of inflammation: the cytokine-hepcidin link [J].
Andrews, NC .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 113 (09) :1251-1253
[5]  
DU XX, 1994, BLOOD, V83, P2023
[6]   Anemia in the elderly: Current understanding and emerging concepts [J].
Eisenstaedt, Richard ;
Pennix, Brenda W. J. H. ;
Woodman, Richard C. .
BLOOD REVIEWS, 2006, 20 (04) :213-226
[7]   Increasing production of homocysteine and neopterin and degradation of tryptophan with older age [J].
Frick, B ;
Schroecksnadel, K ;
Neurauter, G ;
Leblhuber, F ;
Fuchs, D .
CLINICAL BIOCHEMISTRY, 2004, 37 (08) :684-687
[8]  
FUCHS D, 1991, EUR J HAEMATOL, V46, P65
[9]   Inflammatory biomarker, neopterin, enlarges splenic mast-cell-progenitor pool: Prominent impairment of responses in age-related stromal cell-impairment mouse SCI/SAM [J].
Fukumoto, Toshitaka ;
Tsuboi, Isao ;
Harada, Tomonori ;
Hiramoto, Masaki ;
Minami, Akihiro ;
Koshinaga, Morimichi ;
Hirabayashi, Yoko ;
Kanno, Jun ;
Inoue, Tohru ;
Aizawa, Shin .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2006, 6 (12) :1847-1858
[10]   STRUCTURE AND EXPRESSION OF THE MESSENGER-RNA FOR MURINE GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR [J].
GOUGH, NM ;
METCALF, D ;
GOUGH, J ;
GRAIL, D ;
DUNN, AR .
EMBO JOURNAL, 1985, 4 (03) :645-653