Inflammatory cells can either promote or inhibit tumor growth. Here we studied whether CD40, a key molecule for adaptive immune response, has any role in mammary carcinogenesis of BALB/NeuT transgenic tumor-prone mice. We transferred the HER2/neu oncogene into CD40-null background to obtain the CD40-KO/NeuT strain. CD40-KO/NeuT mice showed delayed tumor onset and reduced tumor multiplicity. BM ...

OBJECTIVE It remains elusive how CD40 endocytosis or clustering on the cell surface is induced by different forms of CD40 agonist. This study aims to investigate whether lipid rafts differentially regulate CD40 traffic and signaling in proinflammatory activation of cardiovascular endothelial cells (ECs). METHODS AND RESULTS Using fluorescent microscopy and flow cytometry, we demonstrated that...

While it has long been understood that CD40 plays a critical role in the etiology of autoimmunity, glycobiology is emerging as an important contributor. CD40 signaling is also gaining further interest in transplantation and cancer therapies. Work on CD40 signaling has focused on signaling outcomes and blocking of its ligand, CD154, while little is known about the actual receptor itself and its ...

CD40 is a TNF receptor superfamily (TNFRSF) member central to the development of many aspects of the adaptive immune response. CD40 signaling promotes adaptive immunity in part by inducing the expression of cytokines, chemokines, and various adhesion and co-stimulatory molecules. The family of cytoplasmic adapter proteins, the TNFR-associated factors (TRAFs), serve as major mediators of TNFRSF ...

Anti-beta2glycoprotein I (anti-beta2GPI) antibodies constitute the main autoantibody specificity in the sera of patients with antiphospholipid syndrome (APS). There is evidence that anti-beta2GPI antibodies induce the precoagulant activity of the endothelium by cross-linking the beta2 glycoprotein I (beta2GPI) on the cell surface. Since beta2GPI lacks intracellular domains, homology with other ...

OBJECTIVE Beyond their eminent role in hemostasis and thrombosis, platelets are recognized as mediators of inflammation. Platelet cluster of differentiation 40 (CD40) ligand (CD40L and CD154) plays a key role in mediating platelet-induced inflammation in atherosclerosis. CD40, the receptor for CD40L, is present on platelets; however, the role of CD40 on this cell type is until now undefined. ...

Immune stimulatory monoclonal antibodies are currently evaluated as anti/cancer agents in clinical trials. While overall toxicity seems to be moderate, liver toxicities have been reported and are not completely understood. Based on the observation that CD11bGr-1 MDSC accumulate in the liver of tumor-bearing mice, we decided to study the effect of anti-CD40 treatment on hepatic MDSC and the live...

Ligation of endothelial cell (EC) CD40 induces the expression of several proinflammatory cytokines as well as angiogenesis factors, including vascular endothelial growth factor (VEGF). Moreover, despite the reported importance of CD40 in cell-mediated immunity, little is known of the CD40-induced signaling pathways in EC. In this study, we have investigated the function of the Ras signaling pat...

We have investigated immunohistochemically the expression of CD40 in post-mortem human brain tissues. In control brain, the blood vessels were stained weakly for CD40. Vascular expression of CD40 was enhanced in the lesions of Alzheimer's disease and some other neurological diseases. In such diseases, reactive microglia were also positive for CD40. The results of this study suggest that CD40 ex...

BACKGROUND CD40 has been identified on a variety of cell types, and it plays an important role in adaptive immunity and inflammation. Peritoneal mesothelial cells (PMCs) are the main cell layer that line the peritoneal membrane. Previously we found that CD40 ligand (CD154) is functionally expressed on peritoneal macrophages during continuous ambulatory peritoneal dialysis peritonitis. However, ...