Carbonic anhydrase IX (CA9), a specific molecular marker for renal cell carcinoma (RCC), serves as a potential target for RCC-specific immunotherapy using dendritic cells (DCs). However, pulsing of DCs with CA9 alone is not sufficient for generation of a therapeutic anti-tumour immune response against RCC. In this study, in order ...

Cell fusion into multinucleated giant cells (MGC) is an essential process that contributes to many important biological mechanisms in mammalians. In the bone and immune system, macrophages are endowed with a remarkable potential for cell fusion events as evidenced by their propensity to fuse with other cells and between themselves ...

The outer layer of the human placenta is the multinucleated syncytiotrophoblast. The syncytiotrophoblast is formed by the fusion of mononuclear cytotrophoblasts, and aged syncytiotrophoblast nuclei are extruded into the maternal blood as membrane-enclosed "syncytial nuclear aggregates" that are then eliminated from the maternal circulation. Apoptosis proteins are hypothesized to be ...

Defining the mechanisms underlying the control of mitochondrial fusion and fission is critical to understanding cellular adaptation to diverse physiological conditions. Here we demonstrate that hypoxia induces fission of mitochondrial membranes, dependent on availability of the mitochondrial scaffolding protein AKAP121. AKAP121 controls mitochondria dynamics through PKA-dependent inhibitory phosphorylation of Drp1 ...

Significance. Mitochondrial dynamics and turnover are crucial for cellular homeostasis and differentiation. The removal of damaged mitochondria that could contribute to cellular dysfunction or death is achieved through process of mitochondrial autophagy, i.e. mitophagy. Moreover, mitophagy is responsible for removal of mitochondria during terminal differentiation of red blood cells and ...

We previously reported that interleukin-32 gamma (IL-32γ) has a direct effect on osteoclast differentiation and activation in vitro in the context of receptor activator of NF-κB ligand (RANKL) co-stimulation. However, the stage of osteoclast differentiation at which IL-32γ exerts its effect was not determined. Here, we demonstrated that IL-32γ plays ...

The Fas antigen is a transmembrane receptor that can trigger apoptosis in a variety of somatic cells. Ovarian follicular atresia and luteolysis are thought to occur by apoptosis. To reveal the intracellular signal transduction molecules involved in the process of follicular development in the bovine ovary, Fas gene without the ...

Autophagy is a highly conserved, closely regulated homeostatic cellular activity that allows for the bulk degradation of long-lived proteins and cytoplasmic organelles. Its roles in cancer initiation and progression and in determining the response of tumor cells to anticancer therapy are complicated, and only limited investigation has been conducted on ...

The P2X(7) receptor (P2X(7)R), an ATP-gated ion channel, has been implicated in the process of cell-to-cell fusion into multinucleated macrophages (MA), but its contribution to MA fusion driven by physiological/pathological stimuli is not clearly established. Based on several lines of evidence, we demonstrate that P2X(7)R is critical for the induction ...

Somatic cell nuclear transfer (SCNT) is a powerful tool, not only for producing cloned animals, but also in revealing various early developmental events. However, relatively little is known regarding the biological events and underlying mechanism(s) directly associated with early development of SCNT embryos. Here, we show that production of high-quality ...

Foreign body-type multinucleated giant cells (FBGC), formed by macrophage fusion, are a prominent cell type on implanted biomaterials, although the roles they play at these and other sites of chronic inflammation are not understood. Why lymphocytes are present in this scenario and the effects of fusing macrophages/FBGC on subsequent lymphocyte ...

NF-κB activation is essential for receptor activator for NF-κB ligand (RANKL)-induced osteoclast formation. IL-4 is known to inhibit the RANKL-induced osteoclast differentiation while at the same time promoting macrophage fusion to form multinucleated giant cells (MNG). Several groups have proposed that IL-4 inhibition of osteoclastogenesis is mediated by suppressing the ...

Macroautophagy is a catabolic pathway in eukaryotic cells that has recently been shown to facilitate pathogen detection, pathogen restriction and pathogen-derived antigen presentation to CD4(+) T cells. Due to these protective functions during immune responses, several pathogens, including RNA and DNA viruses, have developed strategies to inhibit autophagosome generation or ...

Regulators of membrane fusion play an important role in phagocytosis as they regulate the focal delivery of endomembrane which is required for optimal internalization of large particles. During internalization of Leishmania promastigotes, the surface glycolipid lipophosphoglycan (LPG) is transferred to the macrophage membrane and modifies its fusogenic properties. In this ...

Mitochondria are highly dynamic organelles that mediate essential cell functions such as apoptosis and cell-cycle control in addition to their role as efficient ATP generators. Mitochondrial morphology changes are tightly regulated, and their shape can shift between small, fragmented units and larger networks of elongated mitochondria. We demonstrate that mitochondrial ...

Programmed cell death, or apoptosis, is one of the fates of the medial edge epithelium (MEE) during palatal fusion. Transforming growth factor β (Tgf-β) signaling (such as Tgf-β3) is required for the disappearance of the MEE, but the relationship between Tgf-β3 and apoptosis remains unclear. Here we show that the ...

Thioredoxin (Trx) is a redox-active protein with anti-inflammatory effects but with a short half life of 1h. Genetic fusion of Trx to human serum albumin (HSA) extended its half life without causing significant loss of its biological activities. HSA-Trx caused a decrease in the number of cells in brochoalveolar lavage ...

Mycobacterium tuberculosis is an intracellular bacterium that persists in phagosomes of myeloid cells. M. tuberculosis-encoded factors support pathogen survival and reduce fusion of phagosomes with bactericidal lysosomal compartments. It is, however, not entirely understood if host factors that mediate endosomal fusion affect M. tuberculosis intracellular localization and survival. Neither is ...

Porphyromonas gingivalis is an oral pathogen highly implicated in chronic periodontitis, a disease characterized by inflammatory destruction of the tooth-supporting alveolar bone and eventually, tooth loss. T-cell innate immune responses are actively involved in this pathological process. Receptor activator of NF-κB Ligand (RANKL) is a cytokine that stimulates bone resorption, ...

We have previously reported that human periodontal ligament (hPDL) cells produced many kinds of cytokines as a result of bacterial stimulation, including stimulation with Porphyromonas gingivalis (P. gingivalis). However, the effects of mechanical stress on cytokine production in hPDL cells stimulated by periodontopathogenic bacteria are not clearly understood. In this ...

Nitrogen-containing bisphosphonates (NBPs) are widely used as anti-bone-resorptive drugs. However, use of NBPs results in inflammatory side-effects, including jaw osteomyelitis. In the present study, we examined the effects of alendronate, a typical NBP, on cytokine production by human peripheral blood mononuclear cells (PBMCs) and gingival fibroblasts incubated with lipid A. ...

Radiolabeled annexin V (ANV) has been widely used for imaging cell apoptosis. Recently, a novel ANV-Kunitz-type protease inhibitor fusion protein, ANV-6L15, was found to be a promising probe for improved apoptosis detection based on its higher affinity to phosphatidylserine (PS) compared to native ANV. The present paper investigates the feasibility ...

This study tested the hypothesis that pregnant female baboons exhibit increased levels of various inflammatory mediators in serum resulting from ligature-induced periodontitis, and that these profiles would relate to periodontal disease severity/extent in the animals. The animals were sampled at baseline (B), mid-pregnancy (MP; two quadrants ligated) and at delivery ...

The human symbiont Bacteroides thetaiotaomicron promotes intestinal function and health, whereas the phylogenetically related pathogen Porphyromonas gingivalis is associated with the chronic oral inflammatory disease periodontitis. Although both B. thetaiotaomicron and P. gingivalis synthesize lipopolysaccharides (LPS) consisting of penta-acylated, monophosphorylated lipid A in addition to immunologically silent, nonphosphorylated lipid A, ...

There is an inverse relationship between pocket depth and pocket oxygen tension with deep pockets being associated with anaerobic bacteria. However, little is known about how the host tissues respond to bacteria under differing oxygen tensions within the periodontal pocket. To investigate the effect of different oxygen tensions upon nuclear ...

Background: The present randomized, double-masked, placebo-controlled, parallel-arm study examines the impact of adjunctive subantimicrobial-dose doxycycline (SDD) on the local inflammatory response through cytokine and chemokine levels in gingival crevicular fluid (GCF) samples from patients with chronic periodontitis. Methods: Forty-six patients with chronic periodontitis received scaling and root planing with or ...

The periodontal pathogen Tannerella forsythia possesses a glycosylated S-layer as an outermost cell decoration. While the S-layer provides a selection advantage to the bacterium in the natural habitat, its virulence potential remains to be investigated. In the present study, the immune responses of human macrophages and gingival fibroblasts upon stimulation ...

Periodontitis is a bacterially induced chronic inflammatory disease. Toll-like receptors (TLRs), which could recognize microbial pathogens, are important components in the innate and adaptive immune systems. Both qualitatively and quantitatively distinct immune responses might result from different bacteria stimulation and the triggering of different TLRs. This study explores the interaction ...

A hallmark of infection with the gram-negative pathogen Porphyromonas gingivalis is the induction of a chronic inflammatory response. P. gingivalis induces a local chronic inflammatory response that results in oral inflammatory bone destruction, which manifests as periodontal disease. In addition to chronic inflammation at the initial site of infection, mounting evidence ...

Porphyromonas gingivalis is a major periodontogenic bacterium and possesses immunostimulatory components, such as lipopolysaccharides (LPS) and fimbriae. The host antimicrobial peptide, LL-37, suppresses proinflammatory responses of immune cells but its effect on human gingival fibroblasts (HGFs) is not known. In this study, we assessed the effect of LL-37 on the ...

The emergence of periodontal medicine increased interest in defining the behaviour of peripheral blood cells in periodontitis subjects in comparison with healthy group. The aim of this study was to evaluate the levels of interleukin (IL)-8, tumour necrosis factor-α (TNF-α), IL-6 and IL-10 released by Escherichia coli lipopolysaccharide (LPS)-stimulated peripheral ...

A major cause of chronic inflammatory periodontal disease is Porphyromonas gingivalis, a non-motile, Gram-negative, rod-shaped, anaerobic bacterium. Within gingival tissue, both macrophages and fibroblasts participate in the immune response to foreign entities by releasing cytokines and expressing molecules to recruit and activate lymphocytes. However, the contribution of gingival macrophages and ...

Porphyromonas gingivalis is considered the major pathogen of periodontal disease, which leads to chronic inflammation in oral tissues. P. gingivalis-produced lipopolysaccharide (LPS) is a key factor in the development of periodontitis. It is established that surfactin produced by Bacillus subtilis confers anti-inflammatory properties. However, the underlying mechanisms responsible for surfactin-induced ...

In healthy periodontal tissue, innate immune responses effectively confine and suppress a bacterial insult. However, a disruption of the host-bacterial equilibrium may produce an overexpression of cytokines and lead to permanent, host-mediated tissue damage. Although such periodontal destruction primarily results from activated immune mechanisms, the site-specific damage suggests that local ...

There is no doubt that plaque bacteria are necessary to initiate disease and drive the chronic inflammatory response in the periodontal tissues. At the same time, there is strong evidence that destructive processes occurring as part of the host inflammatory response are responsible for the majority of the hard- and ...

Periodontal diseases (PD) are chronic infectious inflammatory diseases characterized by the destruction of tooth-supporting structures, being the presence of periodontopathogens required, but not sufficient, for disease development. As a general rule, host inflammatory mediators have been associated with tissue destruction, while anti-inflammatory mediators counteract and attenuate disease progression. With the ...

Porphyromonas gingivalis, a pathogen that causes inflammation in human periodontal tissue, killed silkworm (Bombyx mori, Lepidoptera) larvae when injected into the blood (hemolymph). Silkworm lethality was not rescued by antibiotic treatment, and heat-killed bacteria were also lethal. Heat-killed bacteria of mutant P. gingivalis strains lacking virulence factors also killed silkworms. ...

Periodontitis, a chronic inflammatory disease of the tissues supporting the teeth, is characterized by an exaggerated host immune and inflammatory response to periopathogenic bacteria. Toll-like receptor activation, cytokine network induction, and accumulation of neutrophils at the site of inflammation are important in the host defense against infection. At the same ...

Sappanchalcone has been demonstrated to possess several biological effects. However, the molecular mechanism underlying these effects is not fully understood. In this study, we examined the effects of sappanchalcone on hydrogen peroxide (H(2)O(2))-induced cytotoxicity using human dental pulp (HDP) cells, and lipopolysaccharide (LPS)-induced inflammation using human periodontal ligament (HPDL) cells. ...

OBJECTIVE: Periodontitis is a destructive disease which is likely to be the result of the activities of different microbial complexes. Recently, sulphate-reducing bacteria (SRB) have been detected in the oral cavity, and they have been found to be common inhabitants of sites showing periodontal destruction. The aim of study was ...

Although the complement system is centrally involved in host defense, its overactivation or deregulation (e.g., due to inherent host genetic defects or due to pathogen subversion) may excessively amplify inflammation and contribute to immunopathology. Periodontitis is an oral infection-driven chronic inflammatory disease which exerts a systemic impact on health. This ...

Bacterial fimbriae are an important pathogenic factor. It has been demonstrated that fimbrial protein encoded by fimA gene (FimA fimbriae) of Porphyromonas gingivalis not only contributes to the abilities of bacterial adhesion and invasion to host cells, but also strongly stimulates host innate immune responses. However, FimA fimbriae separated from ...

Porphyromonas gingivalis, a Gram-negative oral anaerobe, is associated with periodontal diseases that, in some form, affect up to 80% of the U.S. population. The organism is highly proteolytic, and noncatalytic adhesin domains of the major proteases, gingipains, are involved in bacterium-host interactions. Recently, we showed that gingipain adhesin peptide A44 ...

Porphyromonas gingivalis (P. gingivalis), an important periodontal pathogen in adult chronic periodontitis, has been reported to colocalize in human atheromatous lesions. We have studied the phagocytosis and survival of P. gingivalis in human monocytes, together with the cellular responses of infected human monocytes. Human monocytes were cocultured with P. gingivalis ...

OBJECTIVE: Periodontitis is a destructive disease which is likely to be the result of the activities of different microbial complexes. Recently, sulphate-reducing bacteria (SRB) have been detected in the oral cavity, and they have been found to be common inhabitants of sites showing periodontal destruction. The aim of study was ...

AIM: We sought to determine whether triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether), an extensively used anti-plaque agent with broad-spectrum anti-microbial activity, with reported anti-inflammatory effects via inhibition of prostaglandin E2 and interleukin 1 (IL-1)beta, could also more broadly suppress multiple inflammatory gene pathways responsible for the pathogenesis of gingivitis and periodontitis. MATERIALS AND METHODS: ...

OBJECTIVE: The purpose of this study was to test the hypothesis that periodontopathic bacteria exert potent proinflammatory effects in human decidua. STUDY DESIGN: The immunostimulatory effects of Gram-positive and negative periodontopathic bacteria and their lipopolysaccharides were tested in human decidual cell cultures in comparison with Escherichia coli. Cytokine production was ...

Periodontitis is a multifactorial polymicrobial infection characterized by a destructive inflammatory process affecting tooth-supporting tissues and resulting in periodontal pocket formation, alveolar bone resorption and, eventually, tooth loss. The continuous challenge of host immune and resident cells by periodontopathogens and their virulence factors, such as lipopolysaccharide (LPS), results in enhanced ...

It has been reported that type I interferons (IFN-α/β) play an important role in innate immune responses against viral and bacterial infections. In this study, we used and examined naturally occurred canine periodontal disease to show the therapeutic efficacy of low dose oral administration (LDOA) of canine IFN-α subtype 4 ...

INTRODUCTION: Periapical inflammation is initiated by insult to the dental pulp and mediated by inflammatory cytokines in the periodontal tissue. On the other hand, the destruction of tissue can be prevented by the suppression of pro-inflammatory cytokine activity. The balance between these cytokines and their counterregulatory molecules has been suggested ...