PURPOSE OF REVIEW: Asthma is an inflammatory respiratory condition with significantly associated morbidity and mortality that is increasing in prevalence. Air pollution is an important factor in both the development of asthma and in asthma exacerbations. Oxidative stress as a result of exposure to air pollution and underlying genetic polymorphisms ...

The mammalian stress response is an integrated physiological and psychological reaction to real or perceived adversity. Glucocorticoids (GCs) are an important component of this response, acting to redistribute energy resources to both optimize survival in the face of challenge and restore homeostasis after the immediate threat has subsided. Release of ...

Post-mortem analyses of human brain tissue samples from patients suffering from neurodegenerative disorders have demonstrated dysfunction of the endoplasmic reticulum (ER). A common characteristic of the aforementioned disorders is the intracellular accumulation and aggregation of proteins due to genetic mutations or exogenous factors, leading to the activation of a stress ...

The success of insects is in large part due to their ability to survive environmental stress, including heat, cold, and dehydration. Insects are also exposed to infection, osmotic or oxidative stress, and to xenobiotics or toxins. The molecular mechanisms of stress sensing and response have been widely investigated in mammalian ...

Takayasu's arteritis (TA) is a chronic, occlusive, inflammatory disease of the aorta, its major branches and the pulmonary arteries. Its etiology remains unclear, although it has been suggested that a variety of antigens from Mycobacterium tuberculosis and probably other mycobacteria may trigger inflammatory pathology either directly in the arterial wall ...

While the factors that regulate the onset and progression of idiopathic pulmonary fibrosis (IPF) are incompletely understood, recent investigations have revealed that endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are prominent in alveolar epithelial cells in this disease. Initial observations linking ER stress and IPF ...

It is well known that psychological stress is associated with increased atherosclerosis. This response is mainly mediated by altered immune reactions due to either activation or depression of the hypothalamic-pituitary-adrenal (HPA) regulatory feed back mechanisms that influence both the vascular endothelium function and the recruitment of circulating monocytes and their ...

Vitiligo is an acquired depigmenting disorder characterized by a chronic and progressive loss of melanocytes from the epidermis and follicular reservoir. The mechanism of melanocyte disappearance has never been clearly understood. This review discussed the data supporting the theory of melanocytorrhagy and apoptosis as one of the primary defects underlying ...

Uncontrolled endoplasmic reticulum (ER) stress responses are proposed to contribute to the pathology of chronic inflammatory diseases such as type 2 diabetes or atherosclerosis. However, the connection between ER stress and inflammation remains largely unexplored. Here, we show that ER stress causes activation of the NLRP3 inflammasome, with subsequent release ...

BACKGROUND: Little is known about the effect of neuropeptides on basophils, which are important effector cells in immune and allergic responses. OBJECTIVE: This study aimed at revealing the role of α-melanocyte-stimulating hormone (α-MSH) on basophil function. METHODS: Expression of melanocortin receptors and proopiomelanocortin (POMC) was analyzed by means of RT-PCR, ...

The liver is an immunocompetent organ that plays a key role in the immune response to infections, and the development of hepatic immune function during early postnatal stages has not been thoroughly characterized. This study analyzed the constitutive expression of complement factors, namely C3 and C9, and pattern recognition receptors, ...

Many biomaterials used in tissue engineering cause a foreign body response in vivo, which left untreated can severely reduce the effectiveness of tissue regeneration. In this study, an anti-inflammatory hormone α-melanocyte stimulating hormone (α-MSH) was physically adsorbed to the surface of biodegradable poly (lactic-co-glycolic) acid (PLGA) microspheres to reduce inflammatory ...

Autoimmune uveitis is an inflammatory disorder of the eye that can lead to pain and vision loss. Steroids and immunosuppressive drugs are currently the only therapeutics for uveitis and have serious ocular and systemic toxicities. Therefore, safer alternative therapeutics are desired. Alpha-melanocyte stimulating hormone (α-MSH) is a neuropeptide that suppresses ...

NF-κB, an important proinflammatory factor, is a crucial regulator of cell survival. Both lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) activate NF-κB signalling. Oestrogens were shown to suppress NF-κB activation. Oestrogens exert a sensitizing action to proapoptotic stimuli such as LPS and TNF-α in anterior pituitary cells. In the present ...

The nucleotide receptor P2X(7) is an attractive therapeutic target and potential biomarker for multiple inflammatory and neurologic disorders, and it is expressed in several immune, osteogenic, and neurologic cell types. Aside from its role in the nervous system, it is activated by ATP released at sites of tissue damage, inflammation, ...

Sigma receptor agonists have been found to provide potent neuroprotection in rats and mice. This neuroprotection is thought to be mediated through anti-excitotoxic mechanisms. Neuroprotective and immune modulatory effects of sigma ligands have not been investigated in embolic stroke. In the present study, rats were subjected to embolic stroke or ...

In the present study, we evaluated the neuroprotection time window for nerve growth factor (NGF) after ischemia/reperfusion brain injury in rabbits as related to this anti-apoptosis mechanism. Male New Zealand rabbits were subjected to 2 h of middle cerebral artery occlusion (MCAO), followed by 70 h of reperfusion. NGF was administered after ...

Damage-associated molecular patterns (DAMPs) initiate inflammatory pathways that are common to both sterile and infectious processes. The DAMP, high-mobility group box 1 (HMGB1), and the transcription factor, interferon regulatory factor 1 (IRF-1), have been independently associated as key players in ischemia-reperfusion (I/R) injury. Our study demonstrates that IRF-1 contributes to ...

Hemorrhagic shock due to trauma (HS/T) induces an inflammatory response that can contribute to end-organ injury. The pathways involved in the initiation and propagation of HS/T-induced inflammation are incompletely understood. Here, we hypothesized that the DNA sensor TLR9 would have a role in inflammatory signaling after HS/T. Using mice expressing ...

Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and cell proliferation. Identification of regulatory proteins that control the switch between apoptotic and alternative DR signaling opens new therapeutic opportunities. ...

Paradoxically, not only proteinases but also their inhibitors can correlate with bad prognosis of cancer patients, underlining the evolving concept of the protease web as the complex interplay between proteinases, their inhibitors and effector molecules. Elevated levels of tissue inhibitor of metalloproteinases-1 (TIMP-1) render the liver more susceptible to metastasis ...

Heme oxygenase (HO)-1 is the inducible isoform of the first and rate-limiting enzyme of heme degradation. HO-1 has potent antioxidant and also anti-inflammatory functions, the underlying mechanisms of which are not well understood. Together with antioxidant carbon monoxide and biliverdin, HO produces reactive iron, which unambiguously connect this enzyme with ...

Systemic activation of the inflammatory immune system contributes to the progression of cirrhosis with ascites. Immune cells become activated after interacting at the mesenteric lymph nodes (MLNs) with bacteria translocated from the gut, and thereafter reach the bloodstream through recirculation. It is unknown whether systemic activation of the immune system ...

Although the innate immune system has been demonstrated to play important roles as the first line of defense against various infections, little is known about the interactions between intrahepatic inflammatory cells and the cytokine network in the liver. Here, we examined the role of IL-18 in IHL recruitment in acute ...

Ischemia/reperfusion injury (IRI) is a common complication after liver surgery. Approximately 10% of grafts lose function in the early stage after liver transplantation. However, there is no effective way against IRI yet. Heat shock protein 27 (HSP27), a member of the heat shock protein families, is recognized as a protective ...

In a fatal mouse model of invasive candidiasis (IC), fungal burden changes with variable dynamics in the kidney, brain, spleen, and liver and declines in all organs except for the kidney, which inexorably loses function. Since leukocytes are required to control Candida, we hypothesized that differential leukocyte infiltration determines organ-specific ...

Not only does the underlying disease that requires surgery constitute a significant stress to the human body, but also the surgery itself serves as a stressor. Cytokine secretion is activated in response to the surgical stress during liver transplantation. We examined 44 patients to compare cytokine levels, according to the ...

Whereas in most cases a fatty liver remains free of inflammation, 10%-20% of patients who have fatty liver develop inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Inflammation may precede steatosis in certain instances. Therefore, NASH could reflect a disease where inflammation is followed by steatosis. In contrast, NASH subsequent to simple ...

Increasing evidence shows that reactive oxygen species (ROS) may be critical mediators of liver damage during the relative hypoxia of ischemia/reperfusion injury (IRI) associated with transplant surgery or of the tissue microenvironment created as a result of chronic hepatic inflammation or infection. Much work has been focused on Kupffer cells ...

Chemokines modulate inflammatory responses that are prerequisites for organ fibrosis upon liver injury. Monocyte-derived hepatic macrophages are critical for the development, maintenance, and resolution of hepatic fibrosis. The specific role of monocyte-associated chemokine (C-X3-C motif) receptor 1 (CX₃CR1) and its cognate ligand fractalkine [chemokine (C-X3-C motif) ligand 1)] in liver ...

The demands that are imposed on the liver as a result of its function as a metabolic organ that extracts nutrients and clears gut-derived microbial products from the blood are met by a unique microanatomical and immunological environment. The inherent tolerogenicity of the liver and its role in the regulation ...

The incidence of obesity has dramatically increased in recent years. Consequently, obesity and associated disorders such as nonalcoholic fatty liver disease (NAFLD) constitute a serious threat. Therefore, the contribution of visceral adipose tissue to metabolic homeostasis has become a focus of interest. Visceral adipose tissue secretes free fatty acids (FFAs) ...

The liver is a complex organ with a unique microcirculation and both synthetic and immune functions. Innate immune responses have been studied in response to single inflammatory mediators and several clinically relevant models of infection and injury. While standard histological techniques have been used in many models, the liver microcirculation ...

Hepatocyte apoptosis plays an important role in the development of fulminant hepatic failure (FHF). The objective of this study was to investigate the antiapoptotic effect of melatonin in an animal model of FHF of viral origin induced by the rabbit hemorrhagic disease virus (RHDV). Rabbits were experimentally infected with 2 × 10(4) ...

Neferine is a major alkaloid component of "Lian Zi Xin", embryos of the seeds of Nelumbo nucifera Gaertner, Nymphaeaceae. Previous studies have shown that neferine has an inhibitory effect on pulmonary fibrosis through its anti-inflammatory and anti-oxidative activities and inhibition of cytokines and NF-κB. However, it is unknown whether neferine ...

Hepatocyte injury is ubiquitous in clinical practice, and the mode of cell death associated with this injury is often apoptosis, especially by death receptors. Information from experimental systems demonstrates that hepatocyte apoptosis is sufficient to cause liver hepatic fibrogenesis. The mechanisms linking hepatocyte apoptosis to hepatic fibrosis remain incompletely understood, ...

Obesity is increasingly being recognized as a risk factor for a number of benign and malignant gastrointestinal conditions. However, literature on the underlying pathophysiological mechanisms is sparse and ambiguous. There is compelling evidence that both overnutrition and undernutrition negatively interfere with the immune system. Overnutrition has been found to increase ...

The mobilization and extracellular release of nuclear high mobility group box-1 (HMGB1) by ischemic cells activates inflammatory pathways following liver ischemia/reperfusion (I/R) injury. In immune cells such as macrophages, post-translational modification by acetylation appears to be critical for active HMGB1 release. Hyperacetylation shifts its equilibrium from a predominant nuclear location ...

Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the United States and other developed countries and is expected to increase in the next few years. Emerging data suggest that some patients with NAFLD may progress to nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. NAFLD ...

Increasing evidence suggests that the presence of endotoxemia is of substantial clinical relevance to patients with cirrhosis, but it is unclear whether and how gut-derived LPS amplifies the tumorigenic response of the liver. We found that the circulating levels of LPS were elevated in animal models of carcinogen-induced hepatocarcinogenesis. Reduction ...

Programmed death-1 (PD-1)/B7-H1 costimulation acts as a negative regulator of host alloimmune responses. Although CD4 T cells mediate innate immunity-dominated ischemia and reperfusion injury (IRI) in the liver, the underlying mechanisms remain to be elucidated. This study focused on the role of PD-1/B7-H1 negative signaling in liver IRI. We used ...

Acetaminophen (APAP) hepatotoxicity is currently the most frequent cause of acute liver failure in the US and many European countries. Although intracellular signalling mechanisms are critical for hepatocellular injury, a contribution of inflammatory cells, especially neutrophils, has been suggested. However, conflicting results were obtained when using immunological intervention strategies. The ...

BACKGROUND: Cytokine changes after microwave tissue ablation (MTA) were compared with hepatic resection, cryotherapy (CRYO), and radiofrequency ablation (RFA). Cytokine production was measured at various ablation volumes for each modality and correlated with the transitional inflammatory zone produced by the ablation techniques. METHODS: Live rats underwent MTA, surgical resection, CRYO ...

To assess the significance of the non-genomic signaling of TCDD (=dioxin) on liver of C57BL/6 mice and HepG2 human hepatoma cells, we first determined the group of markers that are susceptible to inhibition by parthenolide, a compound known to specifically suppress NF-κB-mediated inflammation. Of those, the most consistent marker turned ...

The immunopathogenesis of type I autoimmune hepatitis (AIH-I) might involve the deregulation of different cellular processes. Here, we investigated the liver expression of selected cytokines and genes of regulatory cell populations in children both at diagnosis and during biochemical remission following immunosuppressive treatment (AIH-Ir). We found a higher Vα24, IFN-γ, ...

The Chinese herb modified Yi Guan Jian (mYGJ) is an effective regimen that is usually used in outpatients with chronic liver diseases such as fibrosis and cirrhosis. However, the mechanism for the action of mYGJ on liver fibrosis is not yet clear. In this study, we found that mYGJ induced ...

IL-22 is made by a unique set of innate and adaptive immune cells, including the recently identified noncytolytic NK, lymphoid tissue-inducer, Th17, and Th22 cells. The direct effects of IL-22 are restricted to nonhematopoietic cells, its receptor expressed on the surface of only epithelial cells and some fibroblasts in various ...

Aldehydes that are produced following the breakdown of ethanol (acetaldehyde) and lipid peroxidation of membranes (malondialdehyde) have been shown to bind (adduct) proteins. Additionally, these two aldehydes can combine (MAA) on nonsyngeneic and syngeneic proteins to initiate numerous immune responses to the unmodified part of the protein in the absence ...

The role of hepatocyte apoptosis in the physiopathology of obstructive cholestasis is still controversial. Although some data have strongly suggested that hepatocellular cholestatic injury is due to Fas-mediated hepatocyte apoptosis, some others concluded that necrosis, rather than apoptosis, represents the main type of hepatocyte death in chronic cholestasis. Moreover, it ...

NKT cells are highly enriched within the liver. On activation NKT cells rapidly release large quantities of different cytokines which subsequently activate, recruit, or modulate cells important for the development of hepatic inflammation. Recently, it has been demonstrated that NKT cells can also produce interleukin-17 (IL-17), a proinflammatory cytokine that ...