Thioredoxin reduces C-C chemokine-induced chemotaxis of human eosinophils.
BACKGROUND
Human thioredoxin (TRX) is one of redox-active proteins that regulate reactive oxidative metabolisms. In recent study, we found that serum levels of TRX were elevated in asthmatic patients with exacerbation; however, few details are known about the physiological role of TRX in allergic inflammation, involving eosinophil infiltration.


OBJECTIVE
In the present study, we examined whether TRX modulated C-C chemokine-induced chemotaxis of human eosinophils.


METHODS
Eosinophils were isolated from subjects with mild eosinophilia by modified CD16 negative selection. After incubation with or without recombinant TRX, chemotaxis of human eosinophils was measured using Boyden chamber.


RESULTS
Preincubation with TRX suppressed eotaxin- and regulated on activation, normal T-cell expressed and secreted (RANTES)-induced chemotaxis of eosinophils. Although, TRX had no effect on the expression of C-C chemokine receptor 3, which is a receptor of eotaxin and RANTES, we demonstrated that the activation of extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinases, which play an important role in eosinophil migration, was attenuated by the treatment with TRX.


CONCLUSIONS
Our results suggest that the elicited TRX is beneficial to reduce allergic inflammation through negative regulation of eosinophil functions and has potential in the treatment of allergic diseases, such as asthma.
Kobayashi
N
N
Department of Clinical and Laboratory Medicine, Akita University School of Medicine, Akita 010-8543, Japan.
Yamada
Y
Y
Ito
W
W
Ueki
S
S
Kayaba
H
H
Nakamura
H
H
Yodoi
J
J
Chihara
J
J
D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D019742:Chemokines, CC / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D004802:Eosinophilia / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013879:Thioredoxins / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
D019742:Chemokines, CC; D011994:Recombinant Proteins; C491203:TXN protein, human; D013879:Thioredoxins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases