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Lactoferrin upregulates the expression of CD4 antigen through the stimulation of the mitogen‐activated protein kinase in the human lymphoblastic T Jurkat cell line
Author(s) -
DhenninDuthille Isabelle,
Masson Maryse,
Damiens Eve,
Fillebeen Carine,
Spik Geneviève,
Mazurier Joël
Publication year - 2000
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/1097-4644(20001215)79:4<583::aid-jcb70>3.0.co;2-9
Subject(s) - jurkat cells , lactoferrin , protein kinase a , microbiology and biotechnology , stimulation , mitogen activated protein kinase , antigen , chemistry , t cell , kinase , immunology , biology , biochemistry , immune system , endocrinology
The main biological properties of lactoferrin are thought to concern inflammation and immunomodulation processes, including maturation of immature B and T cells. Lactoferrin accelerates T‐cell maturation by inducing the expression of the CD4 surface marker. In this report, using the Jurkat T‐cell line, we have shown that lactoferrin upregulates the expression of CD4 antigen through the activation of a transduction pathway. Using an anti‐phosphotyrosine antibody, lactoferrin was demonstrated to induce a cascade of phosphorylation of numerous proteins on their tyrosine residues. This tyrosine‐phosphorylation was transient, reaching maxima between 5 and 10 min. We also identified the mitogen‐activated protein kinase (MAP kinase) which presented an enhanced catalytic activity, reaching a maximum at 10 min of incubation with lactoferrin. Moreover, the use of inhibitors such as genistein and PD98059, tyrosine kinases and MAP kinase kinase (or MEK) inhibitors respectively, allowed us to correlate the activation of MAP kinase with the upregulation of CD4 expression. Finally, using Lck‐defective Jurkat cells, our results showed that the p56 lck (Lck) kinase is necessary for MAP kinase activity and CD4 expression. This paper demonstrates that lactoferrin activates transduction pathway(s) in lymphoblastic T‐cells, and that Lck and the Erk2 isoform of MAP kinase are implicated in the upregulation of CD4, induced by lactoferrin in these cells. J. Cell. Biochem. 79:583–593, 2000. © 2000 Wiley‐Liss, Inc.