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 oil PBMCs, LPS stimulation caused I kappa B alpha degradation. Inhibition of NF kappa B activation abrogated LPS-inducecl 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 (IFN gamma) levels in the medium of PBMCs. Neutralization of IFN gamma and IFN gamma receptor using specific antibodies blocked LPS-induced CD40 expression by 44% and 37%, respectively. In summary, LPS-induced CD40 expression oil human PBMCs through activation of NF kappa B and JNK, and partially through the induction of IFN gamma Production. (C) 2008 Elsevier Inc. All rights reserved.