Mechanisms of LPS-induced CD40 expression in human peripheral blood monocytic cells.
CD40 plays important roles in cell-mediated and humoral immune responses. In this study, we explored mechanisms underlying lipopolysaccharide (LPS)-induced CD40 expression in purified human peripheral blood monocytic cells (PBMCs) from healthy volunteers. Exposure to LPS induced increases in CD40 mRNA and protein expression on PBMCs. LPS stimulation caused IkappaBalpha degradation. Inhibition of NFkappaB activation abrogated LPS-induced CD40 expression. LPS stimulation also resulted in phosphorylation of mitogen-activated protein kinases, however, only Jun N-terminal kinase (JNK) was partially involved in LPS-induced CD40 expression. In addition, LPS exposure resulted in elevated interferon gamma (IFNgamma) levels in the medium of PBMCs. Neutralization of IFNgamma and IFNgamma receptor using specific antibodies blocked LPS-induced CD40 expression by 44% and 37%, respectively. In summary, LPS-induced CD40 expression on human PBMCs through activation of NFkappaB and JNK, and partially through the induction of IFNgamma production.
Wu
Weidong
W
Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, 104 Mason Farm Road, Chapel Hill, NC 27599, USA. Weidong_Wu@med.unc.edu
Alexis
Neil E
NE
Bromberg
Philip A
PA
Jaspers
Ilona
I
Peden
David B
DB
D019013:CD40 Antigens / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology* / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism
D019013:CD40 Antigens; D008070:Lipopolysaccharides; D016328:NF-kappa B; D007371:Interferon-gamma; D048670:MAP Kinase Kinase 4