MIP-1alpha induces binding of nuclear factors to the kappaB DNA element in human B cells.
The chemokine macrophage inflammatory protein-1 alpha (MIP-1alpha) stimulates migration of B cells through an unknown mechanism. Furthermore, little is known about signal transduction mechanisms through which MIP-1alpha might signal phenotypic changes in B cells. We are investigating the role of MIP-1alpha in B cell signaling. Here we report that stimulation of the Ramos B cell line or tonsil B or peripheral blood-B (PBL-B) cells with MIP-1alpha caused the transcription factor NF-kappaB to bind to DNA. NF-kappaB induction was dose dependent, and was transient, with peak induction occurring at 30 min. MIP-1alpha treatment stimulated the degradation of IkappaBalpha, a cytoplasmic inhibitor of NF-kappaB. The biological significance of NF-kappaB activation by MIP-1alpha is currently unknown, but it is known that NF-kappaB modulates expression of genes involved in many inflammatory and immune responses. Here we show that NF-kappaB activation is a target of signals sent into B cells by MIP-1alpha.
Omoike
O I
OI
Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, 66045, USA.
Teague
R M
RM
Benedict
S H
SH
Chan
M A
MA
D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017931:DNA Primers; D006801:Humans; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D017931:DNA Primers; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins