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Gao B Seki E Brenner DA Friedman S Cohen JI Nagy L Szabo G Zakhari S 《American journal of physiology. Gastrointestinal and liver physiology》2011,300(4):G516-G525
Excessive alcohol consumption is a leading cause of chronic liver disease in the Western world. Alcohol-induced hepatotoxicity and oxidative stress are important mechanisms contributing to the pathogenesis of alcoholic liver disease. However, emerging evidence suggests that activation of innate immunity involving TLR4 and complement also plays an important role in initiating alcoholic steatohepatitis and fibrosis, but the role of adaptive immunity in the pathogenesis of alcoholic liver disease remains obscure. Activation of a TLR4-mediated MyD88-independent (TRIF/IRF-3) signaling pathway in Kupffer cells contributes to alcoholic steatohepatitis, whereas activation of TLR4 signaling in hepatic stellate cells promotes liver fibrosis. Alcohol consumption activates the complement system in the liver by yet unidentified mechanisms, leading to alcoholic steatohepatitis. In contrast to activation of TLR4 and complement, alcohol consumption can inhibit natural killer cells, another important innate immunity component, contributing to alcohol-mediated acceleration of viral infection and liver fibrosis in patients with chronic viral hepatitis. Understanding of the role of innate immunity in the pathogenesis of alcoholic liver disease may help us identify novel therapeutic targets to treat this disease. 相似文献
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Myocardial ischemia/reperfusion (I/R) is the most common cause of myocardial inflammation, which is primarily a manifestation of the innate immune responses. Innate immunity is activated when pattern recognition receptors (PRRs) respond to molecular patterns common to microbes and to danger signals expressed by injured or infected cells, so called pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The expression of various PRRs in cardiomyocytes and the release of DAMPs from cardiomyocytes subjected to I/R injury, through active mechanisms as well as passive processes, enable cardiomyocytes to generate innate immune responses. Studies in isolated heart and cardiomyocytes have confirmed the inflammatory and functional effects of cardiac PRRs especially Toll-like receptors in response to I/R-derived DAMPs, such as heat shock proteins. This review addresses the active role of cardiomyocytes in mediating innate inflammatory responses to myocardial I/R. We propose that cardiomyocytes act as innate immune cells in myocardial I/R injury. 相似文献
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Di Carlo M 《Immunity & ageing : I & A》2012,9(1):3-8
ABSTRACT: The success of biomedical researches has led to improvement in human health and increased life expectancy. An unexpected consequence has been an increase of age-related diseases and, in particular, neurodegenerative diseases. These disorders are generally late onset and exhibit complex pathologies including memory loss, cognitive defects, movement disorders and death. Here, it is described as the use of simple animal models such as worms, fishes, flies, Ascidians and sea urchins, have facilitated the understanding of several biochemical mechanisms underlying Alzheimer's disease (AD), one of the most diffuse neurodegenerative pathologies. The discovery of specific genes and proteins associated with AD, and the development of new technologies for the production of transgenic animals, has helped researchers to overcome the lack of natural models. Moreover, simple model systems of AD have been utilized to obtain key information for evaluating potential therapeutic interventions and for testing efficacy of putative neuroprotective compounds. 相似文献
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As the human lung is exposed to a variety of microbial pathogens in the environment, a first line of defense is built up by
pulmonary cells like bronchial/alveolar epithelial cells and alveolar macrophages. These cells express several pattern recognition
receptors (PRRs) recognizing highly conserved microbial motifs and initiating the production of chemokines and pro- and anti-inflammatory
cytokines acting as transmembrane or intracellular receptors. This might not only lead to acute but also to chronic inflammation
which is discussed as an underlying mechanism in the pathogenesis of different lung diseases. 相似文献
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Innate immunity in rice 总被引:2,自引:0,他引:2
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Innate immunity in plants: a continuum of layered defenses 总被引:1,自引:0,他引:1
Plant responses to pathogenic invaders result from recognition of nonself elicitors. Host surveillance proteins activate distinct signaling pathways that induce partially overlapping defensive responses. Pathogen virulence is promoted by inhibition of these pathways. This evolutionary struggle has produced plant immune systems that rely on a continuum of layered defenses. 相似文献
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The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at
a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the
response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism
was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long
activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon
linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis,
diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease
progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory
genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance
of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this
system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control
pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens
aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in
early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually
death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control
inflammatory responses and age-related disease development, resulting in an increased chance of long life survival in a "permissive"
environment with reduced pathogen load, medical care and increased quality of life. 相似文献
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Tobin and colleagues show that both inhibition and excessive production of the inflammatory mediator TNFα impact the pathogenesis of tuberculosis (TB) and the response to therapy. Identifying a critical role for the genetically determined balance between pro- and anti-inflammatory eicosanoids in regulating TNFα levels provides a roadmap to tailored TB treatment based on host genotype. 相似文献
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The xenotropic/polytropic subgroup of mouse leukemia viruses (MLVs) all rely on the XPR1 receptor for entry, but these viruses vary in tropism, distribution among wild and laboratory mice, pathogenicity, strategies used for transmission, and sensitivity to host restriction factors. Most, but not all, isolates have typical xenotropic or polytropic host range, and these two MLV tropism types have now been detected in humans as viral sequences or as infectious virus, termed XMRV, or xenotropic murine leukemia virus-related virus. The mouse xenotropic MLVs (X-MLVs) were originally defined by their inability to infect cells of their natural mouse hosts. It is now clear, however, that X-MLVs actually have the broadest host range of the MLVs. Nearly all nonrodent mammals are susceptible to X-MLVs, and all species of wild mice and several common strains of laboratory mice are X-MLV susceptible. The polytropic MLVs, named for their apparent broad host range, show a more limited host range than the X-MLVs in that they fail to infect cells of many mouse species as well as many nonrodent mammals. The co-evolution of these viruses with their receptor and other host factors that affect their replication has produced a heterogeneous group of viruses capable of inducing various diseases, as well as endogenized viral genomes, some of which have been domesticated by their hosts to serve in antiviral defense. 相似文献
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Chiappelli F Prolo P Cajulis KD Angeli A Dovio A Perotti P Pautasso M Sartori ML Saba L Mussino S Fraccalini T Fanto F Manfrini E Mocellini C Rosso MG Grasso E 《Bioinformation》2007,2(1):1-4
The emerging domain of epigenetics in molecular medicine finds application for a variety of patient populations. Here, we present fundamental neuroendocrine immune evidence obtained in patients with senile dementia of the Alzheimer's type (sDAT), and discuss the implications of these data from the viewpoint of translational epigenetics of Alzheimer's disease. We followed 18 subjects with mild sDAT treated with acetylcholinesterase inhibitors, and 10 control subjects matched for age in a repeated measure design every six months for 18 months. We monitored psychosocial profile (Mini-Mental State Examination, Functional Assessment Staging, Independence in Activities of Daily Living, Depression, Profile of Moods States) in parallel to immunophenotypic parameters of T cell subpopulations by flow cytometry. Based on change in the mini-mental state score at entry and at 18 months, patients with sDAT were assigned to a "fast progression" (delta greater than 2 points) or to a "slow progression" group (delta less than or equal to 2 points). The change in circulating activated T cells (CD3+Dr+) with time in patients with sDAT was significantly inversely correlated with the change in time in natural killer (NK) cytotoxic activity to cortisol modulation in these patients, which was greater in patients with fast progression, compared to slow progression sDAT. These data indicate underlying neuroendocrine immune processes during progression of sDAT. Our observations suggest that psychoimmune measures such as those we have monitored in this study provide relevant information about the evolving physiological modulation in patients with sDAT during progression of Alzheimer's disease, and point to new or improved translational epigenetic treatment interventions. 相似文献
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Cerebral amyloid plaques in Alzheimer's disease but not in scrapie-affected mice are closely associated with a local inflammatory process. 总被引:2,自引:0,他引:2
P Eikelenboom J M Rozemuller G Kraal F C Stam P A McBride M E Bruce H Fraser 《Virchows Archiv. B, Cell pathology including molecular pathology》1991,60(5):329-336
Complement proteins of the classical pathway can be immunohistochemically identified in cerebral amyloid plaques in Alzheimer's disease. Microglial cells in and around amyloid plaques express class II major histocompatibility (MHC) antigens and complement receptors CR3 and CR4. Negative immunostaining for immunoglobulins and for T-cell subsets in the brain parenchyma demonstrates a lack of evidence for the involvement of specific immune responses (such as an immune complex-mediated complement activation or a cell-mediated immune response) in cerebral amyloid deposits in Alzheimer's disease. Cerebral amyloid plaques in scrapie-affected mice (slow-virus induced encephalopathy) do not contain complement factors C1q and C3c and are not clustered with microglial cells expressing MHC class II molecules or complement receptor CR3. The data presented suggest the induction of a reactive inflammatory process by beta/A4 amyloid in the human brain, but not by scrapie-induced PrP amyloid in mice. Our findings do not support the hypothesis that the immune system is involved in the generation of amyloid plaques in Alzheimer's disease. 相似文献
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Cells of the innate immune system provide a first line of defense against microbial invaders. Recent studies have revealed how one intriguing member of the innate immune system, the natural killer T cell, is activated during bacterial infections. 相似文献
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Innate versus adaptive immunity in sticklebacks: evidence for trade-offs from a selection experiment 总被引:1,自引:0,他引:1
In vertebrates, the immune system consists of two arms of different characteristics: the innate and the acquired immune response.
Parasites that are only shortly exposed to the immune system are most efficiently attacked by fast, constitutive innate immune
mechanisms. Here, we experimentally selected within four fish families for high innate resistance versus susceptibility of
three-spined sticklebacks (Gasterosteus aculeatus) against infection with the eye-fluke (Diplostomum pseudospathacaeum), a parasite whose metacercariae are protected from the immune system within the eye lens. We predicted that in families
with high susceptibility, the adaptive immune system would be upregulated when challenged with infection. In accordance, we
found that MHC class IIB expression is increased by approximately 50% in those lines selected for higher parasite load (i.e.
low innate response). This suggests extensive genetic correlations between innate and adaptive immune system and/or crosstalk
between both lines of defense. An efficient, specific innate immune response might reduce overall activation of the immune
system and potentially alleviate associated effects of immunopathology. 相似文献
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Innate immunity mediated by TLR5 as a novel antiinflammatory target for cystic fibrosis lung disease
Blohmke CJ Victor RE Hirschfeld AF Elias IM Hancock DG Lane CR Davidson AG Wilcox PG Smith KD Overhage J Hancock RE Turvey SE 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(11):7764-7773
Novel therapies to target lung inflammation are predicted to improve the lives of people with cystic fibrosis (CF) but specific antiinflammatory targets have not been identified. The goal of this study was to establish whether TLR5 signaling is the key molecular pathway mediating lung inflammation in CF, and to determine whether strategies to inhibit TLR5 can reduce the damaging inflammatory response. The innate immune responses were analyzed in both airway epithelial cells and primary PBMCs from CF patients and matched controls. Additionally, 151 clinical isolates of Pseudomonas aeruginosa from CF patients were assessed for motility and capacity to activate TLR5. Blood and airway cells from CF patients produced significantly more proinflammatory cytokine than did control cells following exposure to the CF pathogens P. aeruginosa and Burkholderia cepacia complex (p < 0.001). Stimulation with pure TLR ligands demonstrated that TLR signaling appears to mediate the excessive cytokine production occurring in CF. Using complementary approaches involving both neutralizing Ab targeting TLR5 and flagellin-deficient bacteria, we established that inhibition of TLR5 abolished the damaging inflammatory response generated by CF airway cells following exposure to P. aeruginosa (p < 0.01). The potential therapeutic value of TLR5 inhibition was further supported by our demonstration that 75% of clinical isolates of P. aeruginosa retained TLR5 activating capacity during chronic CF lung infection. These studies identify the innate immune receptor TLR5 as a novel antiinflammatory target for reducing damaging lung inflammation in CF. 相似文献
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