Polyinosinic polycytidylic acid (Poly I:C), an analog of double stranded RNA (dsRNA), can lead to apoptosis in human cancer cells, and have been used as adjuvants to treat cancer patients. Arsenic trioxide (ATO) is used effectively in the treatment of hepatocellular carcinoma (HCC). We sought to evaluate whether Poly I:C ...

Dendritic cells (DCs) are considered the most efficient antigen-presenting cells and are therefore ideal targets for in vivo delivery of antigen for vaccines. We are investigating the strategy of using CD40 ligand (CD40L) as a targeting moiety because this protein has the potential to not only target DCs, but also ...

Objective: Selective progesterone receptor modulators (SPRMs), such as asoprisnil (J867) and ulipristal (CDB-2914), have been shown to reduce fibroid volume in vivo and to induce apoptosis in vitro. CDB-4124 (telapristone), a SPRM with different side groups, also reduced fibroid volume in vivo, and we hypothesized that this SPRM would also ...

In this study, we focused on the effects of a bitter melon (Momordica charantia) leaf extract (BMLE) and a purified component, Kuguacin J (KuJ), on androgen-dependent LNCaP human prostate cancer cells. Both treatments exerted growth inhibition through G1 arrest and induction of apoptosis. In addition, KuJ markedly decreased the levels ...

The activity of α-1,2-mannosidase I is required for the conversion of high-mannose to hybrid-type (ConA reactive) and complex-type N-glycans (Phaseolus vulgaris-leukoagglutinin [PHA-L] reactive) during posttranslational protein N-glycosylation. We recently demonstrated that α-1,2-mannosidase I mRNA decreases in graft-infiltrating CD11c(+) dendritic cells (DCs) prior to allograft rejection. Although highly expressed in immature ...

Candida krusei is a fungal pathogen of interest for the scientific community for its intrinsic resistance to fluconazole. Little is known about the interaction of this yeast with host immune cells. In this work, we have characterized the outcome of the interaction between C. krusei and murine macrophages. Once C. ...

BH3-only protein Bid is a key player in death receptor-induced apoptosis, because it provides the link with the mitochondrial route for caspase activation. In this pathway, Bid is activated upon cleavage by caspase-8. Its BH3 domain-containing carboxy-terminal fragment subsequently provokes mitochondrial outer membrane permeabilization by Bak/Bax activation. Bid has also ...

Neutrophils play a major role in the innate immune system and are normally considered to be short-lived effector cells that exert anti-microbial activity and sometimes immunopathology. Here, we show that these cells possess an additional function as professional antigen-presenting cells capable of priming a T(h)1- and T(h)17-acquired immune response. Using ...

We have recently described the in vitro effects of titanium dioxide (TiO(2)) nanoparticles (NPs) in human neutrophils. The objective of the present study was to determine if TiO(2) NPs induced leukocyte infiltration in the in vivo murine air pouch model of acute inflammation and, if so, to identify which of ...

Camalexin, a major indole phytoalexin of Arabidopsis thaliana, accumulates in various cruciferous plants in response to environmental stress and reportedly displays antimicrobial activities against various plant pathogens. However, its cytotoxicity against eukaryotic cells and potential as a prospective drug for human diseases has been examined only in a limited context. ...

Arctigenin has been demonstrated to have an anti-inflammatory function, but the precise mechanisms of its action remain to be fully defined. In the present study, we determined the effects of arctigenin on lipopolysaccharide (LPS)-induced production of proinflammatory mediators and the underlying mechanisms involved in RAW264.7 cells. Our results indicated that ...

This work summarises current knowledge on how the marine toxin yessotoxin (YTX) induces apoptosis in di_erent types of cells. The work also addresses perspectives for future research on this topic. YTX triggers apoptosis in a variety of cellular systems including cancer cells. The actual apoptotic pathways are not fully understood ...

Overproduction and accumulation of amyloid-β (Aβ) have been proposed to be an initiating factor of neuron loss in Alzheimer's disease (AD). AKT is a pivotal molecule in regulating neuronal survival; however, it is still not known whether upregulation of AKT can protect the cells from the Aβ-induced apoptosis. By using ...

Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with peroxidase and phospholipase A(2) (PLA(2)) activities. Although the cellular function of the peroxidase of Prdx6 has been well elucidated, the function of the PLA(2) of Prdx6 is largely unknown. Here, we report a novel function for the PLA(2) in regulating TNF-induced apoptosis ...

Suppressor of cytokine signaling 1 (SOCS1) has been shown to play important roles in the immune system. It acts as a key negative regulator of signaling via receptors for IFNs and other cytokines controlling T cell development, as well as Toll receptor signaling in macrophages and other immune cells. To ...

We aimed to study the involvement of Kir3.1 channel in TLR4-mediated signaling. LPS stimulation induced the recruitment of TLR4 and Kir3.1 into the lipid raft in THP-1 cells. Treatment with Tertiapin-Q, an inhibitor of Kir3.1, markedly abolished the recruitment of TLR4 into the lipid raft and inhibited the LPS-induced NF-κB ...

Rel/NF-κB transcription factors regulate inflammatory and immune responses. Despite possible subunit redundancy, NF-κB1-deficient (Nfkb1(-/-)) mice were profoundly protected from sterile CD4 T cell-dependent acute inflammatory arthritis and peritonitis. We evaluated CD4 T cell function in Nfkb1(-/-) mice and found increased apoptosis and selectively reduced GM-CSF production. Apoptosis was blocked by ...

Dendritic cells (DCs) are the most professional antigen-presenting cells of the mammalian immune system. They are able to phagocytize, process antigen materials, and then present them to the surface of other cells including T lymphocytes in the immune system. These capabilities make DC therapy become a novel and promising immune-therapeutic ...

Glycogen synthase kinase-3 (GSK-3) is a constitutively active kinase that regulates multiple signaling proteins and transcription factors involved in inflammation. Its role in inflammatory lung diseases, including chronic obstructive pulmonary disease (COPD), is largely unknown. We investigated the role of GSK-3 in the secretion of chemokines and growth factors by ...

The hypothesis that apoptotic factors play a role in the denucleation of erythroblasts has been confirmed by the immunohistological detection of both phosphatidylserine and thrombospondin as phagocytosis-inducing factors in general apoptotic events. Both phosphatidylserine and thrombospondin were detected on the surface of cell membrane of mature erythroblasts, while thrombospondin was ...

Survivin is a multifunctional protein with essential roles in cell division and inhibition of apoptosis, but the molecular underpinnings of its cytoprotective properties are poorly understood. Here we show that homozygous deletion of the aryl hydrocarbon receptor-interacting protein (AIP), a survivin-associated immunophilin, causes embryonic lethality in mice by embryonic day ...

Dendritic cells (DCs) have a critical role in antiviral responses, in autoimmune disease pathogenesis, in initiating and maintaining inflammatory skin disorders and are candidates for cell-based immunotherapeutic approaches for tumours. Recent studies have showed the important role of type I interferons (IFNs) in DC differentiation and activation. In the presence ...

Homoharringtonine (HHT) has been reported to be effective in a portion of patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). To investigate its mechanism of action, cell growth inhibition and cytotoxicity of HHT were investigated in three AML cell lines, HL-60, NB4, and U937, and in three ...

Pancreatic ß-cells have a deficit of scavenging enzymes as catalase (Cat) and glutathione peroxidase (GPx) and therefore are susceptible to oxidative stress and apoptosis. Our previous work showed that in the absence of cytosolic GPx in insulinoma RINm5F cells, an intrinsic activity of 12 lipoxygenase (12(S)-LOX) converts 12S-hydroperoxyeicosatetraenoic acid (12(S)-HpETE) ...

Transglutaminase 2 (TG2) is a protein crosslinking enzyme with several additional biochemical functions. Loss of TG2 in vivo results in impaired phagocytosis of apoptotic cells and altered proinflammatory cytokine production by macrophages engulfing apoptotic cells leading to autoimmunity. It has been proposed that TG2 acts as an integrin β(3) coreceptor ...

Salmonella survives in macrophages by using a molecular syringe to deliver proteins into the host-cell cytosol where they manipulate phagocyte physiology. Arpaia and colleagues (Arpaia et al., 2011) show that deployment of this virulence factor is triggered by the very responses that are intended to confer host resistance.

Corneal grafting is the most prevalent form of transplantation. Corneal endothelial cells (ECs), which form a monolayer of the cornea with minimal proliferative potential, are pivotal for maintenance of corneal clarity. Loss of EC viability and apoptosis leads to graft failure posttransplantation and reduces the quality of donor corneas in ...

BACKGROUND: Macrophages can polarize in which M1/classically activated and M2/alternatively activated macrophages are considered to be the extremes. M1 macrophages are involved in inflammatory reactions, while M2 macrophages are suggested to be involved in homeostasis, parasite killing, tumor promotion, tissue remodeling and in allergic reactions. We hypothesized that polarization of ...

Disruption of the PD-1 pathway leads to breakdown of peripheral tolerance and initiation of autoimmunity. The molecular pathways that mediate this effect remain largely unknown. We report here that PD-1 knockout (PD-1(-/-) ) mice develop more severe and sustained antigen-induced arthritis (AIA) than wild-type (WT) animals, which is associated with ...

The NF-κB transcription factor regulates numerous immune responses but its contribution to interleukin-17 (IL-17) production by T cells is largely unknown. Here, we report that IL-17, but not interferon-γ (IFN-γ), production by γδ T cells required the NF-κB family members RelA and RelB as well as the lymphotoxin-β-receptor (LTβR). In contrast, LTβR-NF-κB ...

Plants have evolved various means for controlled and organized cell destruction, known as programmed cell death (PCD). In plant immune responses against microbial infection, hypersensitive cell death as a form of PCD is a crucial event to prevent the spread of biotrophic pathogens. Recent live cell imaging techniques have revealed ...

The evolution of the immune system to combat infectious disease is inextricably linked to the concomitant risk of autoimmunity. Central to the immune response in both scenarios is T cell-dependent antibody production. Thus, understanding the fundamentals of this process has important applications in both infectious and autoimmune or inflammatory disease. ...

Recent studies have shown that the cellular immune response to the hypoxic microenvironment constructed by vascular remodeling development modulates the resulting pathologic alterations. A major mechanism mediating adaptive responses to reduced oxygen availability is the regulation of transcription by hypoxia-inducible factor 1 (HIF-1). Impairment of HIF-1-dependent inflammatory responses in T ...

BACKGROUND: Imatinib mesylate (STI571), a protein tyrosine kinase inhibitor, was shown to reduce the viability of several cancer cell lines via apoptosis induction; however, the role of reactive oxygen species (ROS) in STI571-induced melanoma cell apoptosis is still undefined. OBJECTIVE: In this study, we investigated the contribution of ROS to ...

We have shown previously that garlic constituent diallyl trisulfide (DATS) inhibits growth of cultured and xenografted human prostate cancer cells in association with apoptosis induction, but the mechanism of cell death is not fully understood. The present study systematically investigates role of inhibitor of apoptosis (IAP) family proteins in regulation ...

Vitamin A and its metabolite, retinoic acid (RA) are implicated in the regulation of immune homeostasis via the peripheral induction of regulatory T cells. Here we showed RA was also required to elicit proinflammatory CD4(+) helper T cell responses to infection and mucosal vaccination. Retinoic acid receptor alpha (RARα) was the critical ...

Respiratory insufficiency is the major cause of morbidity and mortality in patients affected by cystic fibrosis (CF). An excessive neutrophilic inflammation, mainly orchestrated by the release of IL-8 from bronchial epithelial cells and amplified by chronic bacterial infection with Pseudomonas aeruginosa, leads to progressive tissue destruction. The anti-inflammatory drugs presently ...

Impaired neurological development in premature infants frequently arises from periventricular white matter injury (PWMI), a condition associated with myelination abnormalities. Recently, exposure to hyperoxia was reported to disrupt myelin formation in neonatal rats. To identify the causes of hyperoxia-induced PWMI, we characterized cellular changes in the white matter (WM) using ...

Mature B cells generate protective immunity by undergoing immunoglobulin (Ig) class switching and somatic hypermutation, two Ig gene-diversifying processes that usually require cognate interactions with T cells that express CD40 ligand. This T cell-dependent pathway provides immunological memory but is relatively slow to occur. Thus, it must be integrated with ...

Renal infiltration with mononuclear cells is associated with poor prognosis in systemic lupus erythematosus. A renal macrophage/dendritic cell signature is associated with the onset of nephritis in NZB/W mice, and immune-modulating therapies can reverse this signature and the associated renal damage despite ongoing immune complex deposition. In nephritic NZB/W mice, ...

Urinary tract infections (UTI) are one of the most common infectious diseases worldwide. The majority is caused by uropathogenic E. coli. Emerging resistances against conventional antimicrobial therapy requires novel treatment strategies. Beside its role in erythropoiesis, erythropoietin has been recognized to exert tissue-protective and immunomodulatory properties. Here, we investigated the ...

The evolutionarily conserved immune system of the zebrafish, in combination with its genetic tractability, position it as an excellent model system to elucidate the origin and function of vertebrate immune cells. We recently reported the existence of antigen-presenting mononuclear phagocytes in zebrafish, namely macrophages and dendritic cells, but have been ...

Upregulation of cytokines and chemokines is a frequent finding in multiple myeloma (MM). CCL3 (also known as MIP-1α) is a pro-inflammatory chemokine, levels of which in the MM microenvironment correlate with osteolytic lesions and tumor burden. CCL3 and its receptors, CCR1 and CCR5, contribute to the development of bone disease ...

Although cisplatin is one of the most efficient chemotherapeutic agents for the treatment of solid tumors, frequently observed nephrotoxicity has limited its use in several patients. Materials and methods: The protective effect of Glycine max (GM) and Chrysanthemum indicum (CM) extracts on cisplatin-induced apoptosis in human proximal tubular HK-2 cells ...

TNF/iNOS-producing (Tip) dendritic cells have been shown to arise during inflammation and are important mediators of immune defense. However, it is still relatively unclear which cell types contribute to their differentiation. Here we show that CD8 T-cells, through the interaction with DCs, can induce the rapid development of human monocytes ...

Nephrin (NPHS1) has been described as an important structural protein of kidney podocytes. Mutations in this gene lead to the Finnish type congenital nephrotic syndrome. More recently, a role of nephrin as a signalling molecule in kidney podocytes has been identified. Here we show that nephrin has not only a ...

Chronic obstructive pulmonary disease (COPD) is currently the fifth leading cause of death worldwide. Exposure to cigarette smoke (CS) is the primary factor associated with the COPD development. CS activates epithelial cells to secrete chemokines such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) that recruit neutrophils and macrophages to ...

The FcγRs found on macrophages (Ms) and dendritic cells (DCs) efficiently facilitate the presentation or cross-presentation of immune-complexed Ags to T cells. We found that the MHC class I-related neonatal FcR for IgG (FcRn) in both Ms and DCs failed to have a strong effect on the cross-presentation of immune ...

Aim:To investigate the effect of genipin on apoptosis in human leukemia K562 cells in vitro and elucidate the underlying mechanisms.Methods:The effect of genipin on K562 cell viability was measured using trypan blue dye exclusion and cell counting. Morphological changes were detected using phase-contrast microscopy. Apoptosis was analyzed using DNA ladder, ...

To study the role of gram-positive and gram-negative bacteria in the pathogenesis of liver injury, specifically the activation of inflammatory mediators. Peripheral blood mononuclear cells of 20 out-patients were studied, 10 of them with cirrhosis. Peripheral blood mononuclear cells were isolated and exposed to lipopolysaccharide or lipoteichoic acid. CD14, Toll-like ...