Ninety percent of anal cancer is associated with human papilloma viruses (HPVs). Using our previously established HPV transgenic mouse model for anal cancer, we tested the role of the individual oncogenes E6 and E7. K14E6 and K14E7 transgenic mice were treated with dimethylbenz[a]anthracene (DMBA) to the anal canal and compared ...

BACKGROUND:: Sepsis impairs hypoxic pulmonary vasoconstriction (HPV) in patients and animal models, contributing to systemic hypoxemia. Concentrations of cysteinyl leukotrienes are increased in the bronchoalveolar lavage fluid of patients with sepsis, but the contribution of cysteinyl leukotrienes to the impairment of HPV is unknown. METHODS:: Wild-type mice, mice deficient in ...

The anti-inflammatory activities of kakkalide, a major constituent of the flower of Pueraria thunbergiana, and irisolidone, a metabolite of kakkalide produced by intestinal microflora, against carrageenan-induced inflammation in air pouches on the backs of mice and in lipopolysaccharide (LPS)-stimulated peritoneal macrophages were investigated. Kakkalide and irisolidone down-regulated the gene expression ...

Cutaneous beta human papillomavirus (HPV) types appear to be involved in the development of non-melanoma skin cancer (NMSC); however, it is not entirely clear whether they play a direct role. We have previously shown that E6 and E7 oncoproteins from the beta HPV type 38 display transforming activities in several ...

To investigate the role of reactive oxygen species (ROS) as the prime initiators of the angiogenic response after alkali injury of the cornea and observe the effects of antioxidants in preventing angiogenesis. The corneal epithelia of SOD-1-deficient mice or wild-type (WT) mice were removed after application of 0.15 N NaOH ...

Studies have shown that administration of 17β-estradiol prevents trauma-hemorrhage-induced increase in proinflammatory cytokine production by Kupffer cells and associated multiple organ injury. Since activation of peroxisome proliferator-activated receptor γ (PPARγ) following ischemic conditions has been shown to be protective, we examined if PPARγ plays any role in the salutary effects ...

Hypertonic saline (HTS) is useful in the management of intracranial hypertension and shock patients. The aim of this study was to investigate whether HTS enhances host defense in burn mice through the increase of Toll-like receptors (TLRs) and nuclear factor κB (NF-κB) activation. C57BL/6, TLR4, C3H/HeN, and C3H/HeJ (nonfunctional TLR4 ...

Human papilloma virus (HPV) is the principal etiological agent of cervical cancer in women, and its DNA is present in virtually all of these tumors. However, exposure to the high-risk HPV types alone is insufficient for tumor development. Identifying specific collaborating factors that will lead to cervical cancer remains an ...

Atherosclerosis is a chronic inflammatory process occurring in the walls of arteries, in large part due to the accumulation of inflammatory cells. This study was conducted to determine the effect of nuclear factor (NF)-κB decoy oligodeoxynucleotide (ODN) in an atherosclerosis animal model. The mice received i.p. injections of lipopolysaccharide (LPS, ...

18β-Glycyrrhetinic acid (GA) is a natural anti-inflammatory compound derived from licorice root extract (Glycyrrhiza glabra). The effect of GA on experimental periodontitis and its mechanism of action were determined in the present study. Periodontitis was induced by oral infection with Porphyromonas gingivalis W83 in interleukin-10-deficient mice. The effect of GA, ...

In this study, we investigated the therapeutic effect of artemisinin (Art) on lupus nephritis mice and its mechanisms by comparing the differences between lupus nephritis (LN) mice given Art and control mice in molecular biology, immunohistochemistry, and histopathology. The results showed that Art could remarkably relieve the symptoms, decrease the ...

Zinc (Zn)-deficiency (ZD) is implicated in the pathogenesis of human oral-esophageal cancers. Previously, we showed that in ZD mice genetic deletion of cyclooxygenase-2 (Cox-2) enhances N-nitrosomethylbenzylamine-induced forestomach carcinogenesis. By contrast, Cox-2 deletion offers protection in Zn-sufficient (ZS) mice. We hypothesize that ZD activates pathways insensitive to COX-2 inhibition, thereby promoting ...

Tumor necrosis factor (TNF)-α, a homotrimeric, pleiotropic cytokine, is secreted in response to inflammatory stimuli in diseases such as rheumatoid arthritis and inflammatory bowel disease. TNF-α mediates both apoptosis and inflammation, stimulating an inflammatory cascade through the non-canonical pathway of NF-κB activation, leading to increased nuclear RelB and p52. In ...

We investigated the effects of high-fat diet-induced obesity on vascular proinflammatory factors and oxidative stress on endothelium-dependent relaxation of the aorta. Female Swiss mice were submitted to a high-fat diet for 16 weeks. At the end of the experimental period, we evaluated blood pressure, relaxation in response to acetylcholine in ...

To observe the expression of nucleotide-binding oligomerization domain 2 (NOD2) in rats with acute pancreatitis (AP). Sprague-Dawley rats were randomly divided into sham operation (SO) groups and AP groups. Acute pancreatitis was induced with retrograde infusion of sodium taurocholate into the biliopancreatic duct. They were then killed at 3, 6, ...

It is not clear whether interstitial fibroblasts or tubular epithelial cells are primarily responsible for the profibrotic effects of NF-κB activation during renal fibrogenesis. Here, we crossed mice carrying a conditional IκB dominant-negative transgene (IκBdN) with mice transgenic for cell-specific FSP1.Cre (FSP1(+) fibroblasts) or γGT.Cre (proximal tubular epithelia) and challenged ...

Vitamin D(3) upregulated protein 1 (VDUP1) is a candidate tumor suppressor, the expression of which is dramatically reduced in various tumor tissues. In this study, we found that VDUP1 expression is suppressed during human hepatic carcinogenesis, and mice lacking VDUP1 are much more susceptible to diethylnitrosamine-induced hepatocarcinogenesis compared with wild ...

Chemical examination of the stems and twigs of the mangrove plant Excoecaria agallocha L. resulted in the isolation of six ent-kaurane diterpenoids named agallochaols K-P (1-6), an atisane-type diterpenoid agallochaol Q (7), along with eight known diterpenoids (8-15). Their structures were elucidated on the basis of extensive spectroscopic analysis and ...

TLRs play an essential role in the induction of immune responses by detecting conserved molecular products of microorganisms. However, the function of TLR8 is largely unknown. In the current study, we investigated the role of TLR8 signaling in immunity in mice. We found that Tlr8(-/-) DCs overexpressed TLR7, were hyperresponsive ...

Background: Sepsis continues to be a leading cause of morbidity and mortality in newborns. Objective: As both nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) appear to be critical mediators in inflammatory response, we studied the effects of lipopolysaccharide (LPS) on expression and function of NF-κB and p38 ...

The activation of pro-inflammatory gene programs by nuclear factor-kappaB (NF-kappaB) is primarily regulated through cytoplasmic sequestration of NF-kappaB by the inhibitor of kappaB (IkappaB) family of proteins. IkappaBbeta, a major isoform of IkappaB, can sequester NF-kappaB in the cytoplasm, although its biological role remains unclear. Although cells lacking IkappaBbeta have ...

The rhizome of Salvia miltiorrhiza Bunge (SM, family Labiatae), which contains tanshinones as main constituents, has been used as a cardiovascular and anti-inflammatory agent in Chinese medicine. This study aimed to elucidate anti-allergic effects of the root of Salvia miltiorrhiza Bunge (SM, family Labiatae) and its main constituents, tanshinones, against ...

High levels of proinflammatory cytokines are linked to pathogenesis of diarrhea in inflammatory bowel disease (IBD). Na(+) absorption is compromised in IBD. The studies were designed to determine the effect of tumor necrosis factor-α (TNF-α) on the expression and activity of NHE2, a Na(+) /H(+) exchanger (NHE) that is involved ...

NF-kappaB is well established as a key component of the inflammatory response. However, the precise mechanisms through which NF-kappaB activation contributes to inflammatory disease states remain poorly defined. To test the role of NF-kappaB in inflammation, we created a knock-in mouse that expresses a constitutively active form of NF-kappaB p65 ...

The objective of this study was to identify porcine reproductive and respiratory syndrome virus (PRRSV)-encoded proteins that are responsible for the inhibition of TNF-α expression and the mechanism(s) involved in this phenomenon. Using a TNF-α promoter reporter system, the non-structural protein 1 (Nsp1) was found to strongly suppress the TNF-α ...

Tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1β) are elevated in the vitreous of diabetic patients and in retinas of diabetic rats associated with increased retinal vascular permeability. However, the molecular mechanisms underlying retinal vascular permeability induced by these cytokines are poorly understood. In this study, the effects of IL-1β ...

The ADP-ribosyl cyclase activity of CD38, a membrane protein expressed in human airway smooth muscle (ASM) cells, generates cyclic ADP-ribose (cADPR), a Ca²(+)-mobilizing agent. cADPR-mediated Ca²(+) responses to agonists are augmented in human ASM cells by TNF-α. CD38-deficient mice fail to develop airway hyperresponsiveness following intranasal TNF-α or IL-13 challenge, ...

Lanthanide ions have been proven to have various biologic effects. Lanthanum with extremely active physical and chemical property was evidenced to possess antibacterial and immune adjustment effects. In the present study, the anti-inflammatory effects of lanthanum chloride (LaCl(3)) on lipopolysaccharide (LPS)-challenged mice were examined in vivo and in vitro. The ...

In recent years, certain anesthetics have been shown to have protective effects against acute inflammation in experimental animals, an observation that may yield new options for adjunctive treatment of acute inflammation. In this study, we investigated the effects of chloral hydrate (CH) on the acute inflammatory response in BALB/c mice ...

The anti-inflammatory effects of cyanidin-3-O-beta-D-glycoside (C3G), a major constituent of black rice (BR), and its metabolites, cyanidin and protocatechuic acid (PA), were assessed in lipopolysaccharide (LPS)-induced RAW 264.7 cells and carrageenan-induced inflammation in air pouches in BALB/c mice. BR, C3G and its metabolites suppressed the production of the proinflammatory cytokines, ...

The E2 polyubiquitin-conjugating enzyme Ubc13 is a mediator of innate immune reactions. Ubc13 mediates the conjugation of keratin (K)63-linked polyubiquitin chains onto TNF receptor-associated factor 6 and IKKγ during NF-κB activation. In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes. Although Ubc13 has been shown ...

Peroxisome proliferator-activated receptor-γ (PPARγ) agonists, a new class of antidiabetic agents, have been shown to possess antiinflammatory activity. In this study, we investigated the molecular mechanism by which PPARγ agonists inhibit proinflammatory cytokine expression in rat glomerular mesangial cells. Both natural and synthetic PPARγ agonists potently inhibited RANTES (regulated upon ...

This study was designed to detect the role of Toll-like receptor 4 (TLR4) signaling in the dysfunction of cardiac microvascular endothelial cells (CMECs) after hypoxia/reoxygenation (H/R). The cell viability of CMECs was measured by MTT assay. The migration of CMECs was detected by cell scratch wound assay. The expressions of ...

The intestinal epithelium forms a protective barrier against luminal contents and the external environment, mediated via intercellular tight junctions (TJs). The TJ can be disrupted via cell signalling induced by either enteric pathogens or pro-inflammatory cytokines, thereby contributing to various intestinal disorders ranging from acute infectious diarrhoea to chronic inflammatory ...

Mucin hypersecretion is an important clinical feature of several respiratory diseases, including asthma, cystic fibrosis, nasal allergy, rhinitis, and sinusitis. It has been shown that α-melanocyte-stimulating hormone (α-MSH), a proopiomelanocortin (POMC)-derived peptide, has immunomodulatory activities by inhibiting NF-κB activation induced by proinflammatory cytokines such as TNF-α. Because MUC5AC expression is ...

This study was designed to identify the inhibitory effect of rebamipide on tumor necrosis factor-α (TNF-α)-induced interleukin-8 (IL-8) production and nuclear factor-κB (NF-κB) activation in human umbilical vein endothelial cells (HUVECs). After stimulation with TNF-α, HUVECs were treated with rebamipide in a dose-dependent manner. The viability of HUVECs was assessed ...

This study has found that dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; DMC), a naturally occurring chalcone, showed potent anti-inflammatory effects in vitro and in vivo. In a cellular model of inflammation, DMC inhibited production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and attenuated expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-1 ...

Inflammation is tightly regulated by nuclear factor-kappa B (NF-kappaB), and if left unchecked excessive NF-kappaB activation for cytokine overproduction can lead to various pathogenic consequences including carcinogenesis. A proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), can be used to explore possible mechanisms whereby unknown functional pathways modulate the NF-kappaB activity for ...

Elevated levels of Oncostatin M (OSM), an interleukin-6 family cytokine, have been observed in multiple sclerosis (MS), HIV-associated neurocognitive disorder (HAND), and glioblastoma (GBM); however, its effects within the CNS are not well understood. OSM regulates gene expression primarily by activating the JAK/STAT, NF-kappaB, and/or MAPK pathways, in a cell-type ...

A significantly increased risk for dominant sensorineural deafness in patients who have Hirschsprung disease (HSCR) caused by endothelin receptor type B and SOX10 has been reported. Despite the fact that c-RET is the most frequent causal gene of HSCR, it has not been determined whether impairments of c-Ret and c-RET ...

AIM: To investigate the anti-inflammatory effect of Z-ligustilide (LIG) on lipopolysaccharide (LPS)-activated primary rat microglia. METHODS: Microglia were pretreated with LIG 1 h prior to stimulation with LPS (1 microg/mL). After 24 h, cell viability was tested with MTT, nitric oxide (NO) production was assayed with Griess reagent, and the ...

Vitamin D receptor (VDR) plays an essential role in gastrointestinal inflammation. Most investigations have focused on the immune response; however, how bacteria regulate VDR and how VDR modulates the nuclear factor (NF)-kappaB pathway in intestinal epithelial cells remain unexplored. This study investigated the effects of VDR ablation on NF-kappaB activation ...

Tumor necrosis factor-alpha (TNF-alpha) is a key regulator of adipose tissue mass, but mechanisms underlying this effect have not been fully elucidated. We found that exposure to TNF-alpha caused a significant decrease in the number of adipocytes, but not preadipocytes. Subsequent experiments revealed that TNF-alpha selectively deleted adipocytes through induction ...

A20 is a nuclear factor kappaB (NF-kappaB) target gene that encodes a ubiquitin-editing enzyme that is essential for the termination of NF-kappaB activation after tumor necrosis factor (TNF) or microbial product stimulation and for the prevention of TNF-induced apoptosis. Mice lacking A20 succumb to inflammation in several organs, including the ...

Medicarpin, a pterocarpan class of naturally occurring benzopyran furanobenzene compound was synthesized in gram scale to investigate its effects on murine bone cells and in ovariectomized (OVx) mice. Medicarpin, at as low as 10(-10)M suppressed osteoclastogenesis in bone marrow cells (BMCs). Medicarpin-induced apoptosis of mature osteoclasts isolated from long bones. ...

The anti-inflammatory effects of cyanidin-3-O-beta-D-glycoside (C3G), a major constituent of black rice (BR), and its metabolites, cyanidin and protocatechuic acid (PA), were assessed in lipopolysaccharide (LPS)-induced RAW264.7 cells and carrageenan-induced inflammation in air pouches in BALB/c mice. BR, C3G and its metabolites suppressed the production of the proinflammatory cytokines, TNF-alpha ...

In an earlier study, we found that Antrodia camphorata inhibited the production of lipopolysaccharide (LPS)-induced cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 by blocking nuclear factor-kappaB (NF-kappaB) activation in cultured RAW 264.7 macrophages. This study was aimed at evaluating the inhibitory effects of the fermented culture broth of A. camphorata ...

It has been reported that Rhusverniciflua exhibits anti-inflammatory, anti-oxidant and anti-cancer activities. However, little is known about biological activity of sulfuretin, a flavonoid isolated from R.verniciflua. In the present study, we investigated the anti-inflammatory effect and the underlying molecular mechanisms of sulfuretin in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Sulfuretin dose-dependently ...

The objective of this study was to determine the kinetics of nuclear factor-kappa B (NF-kappaB) activation and cytokine expression in bone marrow (BM) cells of exposed mice as a function of the dose rate of protons. The cytokines included in this study are pro-inflammatory [i.e., tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta ...

In recent years, certain anesthetics have been shown to have protective effects against acute inflammation in experimental animals, an observation that may yield new options for adjunctive treatment of acute inflammation. In this study, we investigated the effects of chloral hydrate (CH) on the acute inflammatory response in BALB/c mice ...