Gene expression profiles of peripheral and cord blood mononuclear cells altered by thymic stromal lymphopoietin.
Thymic stromal lymphopoietin (TSLP) was reported to induce dendritic cells to produce Th2-attracting chemokines, followed by allergic inflammation through stimulating not only CD4-positive T cells but also CD8-positive T cells. Therefore, in this experiment, GeneChip and hierarchical clustering were applied to screen the molecules in whole immunity triggered by TSLP directly and indirectly using both adult peripheral and cord blood mononuclear cells as well as isolated monocytes. Gene expression profiles screened a variety of molecules that are triggered by TSLP with or without CD40 ligation. In the profile, RNA expressions of indoleamine 2,3-dioxygenase, that is known to induce anergy of T cells and natural killer cells in protecting fetal rejection; many kinds of proteasomes that were reported to trigger cytokine production by inhibiting suppressors of NF-kappaB; and several kinds of chemokines increased, whereas RNA expression of superoxide dismutase 1 decreased, which was unexpected but considered worthy of notice. Expression of chemokines at protein levels and enzymatic activity of indoleamine 2,3-dioxygenase was further confirmed to increase in the presence of TSLP using ELISA and HPLC, respectively. These results suggest that the advent of microarray technology may enable us to screen novel molecular targets to treat TSLP-related allergic inflammation.
Urashima
Mitsuyoshi
M
Division of Clinical Research and Development, Jikei University School of Medicine, Tokyo, Japan. urashima@jikei.ac.jp
Sakuma
Mio
M
Teramoto
Satoshi
S
Fuyama
Yuichi
Y
Eto
Yoshikatsu
Y
Kondo
Kazuhiro
K
Tanaka
Tadao
T
D000328:Adult; D000818:Animals; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D014366:Tryptophan Oxygenase / Q000235:genetics; D000094632:Thymic Stromal Lymphopoietin
D019013:CD40 Antigens; D018925:Chemokines; D016207:Cytokines; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase; D000094632:Thymic Stromal Lymphopoietin