Experientia supplementum (2012)最新文献

Lung diseases are common and significant causes of illness and death around the world. Inflammasomes have emerged as an important regulator of lung diseases. The important role of IL-1 beta and IL-18 in the inflammatory response of many lung diseases has been elucidated. The cleavage to turn IL-1 beta and IL-18 from their precursors into the active forms is tightly regulated by inflammasomes. In this chapter, we structurally review current evidence of inflammasome-related components in the pathogenesis of acute and chronic lung diseases, focusing on the "inflammasome-caspase-1-IL-1 beta/IL-18" axis.

The current chapter focuses on the role of inflammasome in cancer prevention and development. Emerging evidence suggested that inflammasome is closely correlated with elevated levels of IL-1β and IL-18, activation of NF-κB signaling, enhanced mitochondrial oxidative stress, and activation of autophagic process in cancer. Meanwhile, inflammasome component NOD-like receptors (NLRs) are also involved in carcinogenesis and closely correlated to chemoresponse and prognosis. Although several lines indicated the duplex role of inflammasome in cancer development, the phenomenon might be attributed to NLR difference, cell and tissue type, cancer stage, and specific experimental conditions. Designation of inflammasome targeting strategy has become a novel tool for cancer prevention or treatment.

Traumatic injury as one of the world's most relevant but neglected health concerns results in modulated inflammasome activity, which is closely linked to the development of post-injury complications. Cytokine-producing capacity of cells is important for the appropriate immune response to trauma and requires not only synthesis and transcription of inflammasome components but also their activation. Unfortunately, the precise role of inflammasome in trauma is still largely unknown. However, in the following chapter, we provide an overview on the best described inflammasomes in the various settings of trauma, introducing the recent findings on the up-to-date best described NLRP inflammasomes and underlying cytokines in the inflammatory response to trauma.

Damage-associated molecular patterns (DAMPs) or alarmins are endogenous danger signals that are derived from damaged cells and extracellular matrix degradation, capable of triggering innate immune response to promote tissue damage repair. Hemolytic or hemorrhagic episodes are often associated with inflammation, even when infectious agents are absent, suggesting that damaged red blood cells (RBCs) release DAMPs.Hemoglobin (Hb) composes 96% of the dry weight of RBCs; therefore upon hemolysis, tremendous amounts of Hb are released into the extracellular milieu. Hb oxidation occurs outside the protective environment of RBCs, leading to the formation of different Hb oxidation products and heme. Heme acts as a prototypic DAMP participating in toll-like receptor as well as intracellular nucleotide-binding oligomerization domain-like receptor signaling. Oxidized Hb forms also possess some inflammatory actions independently of their heme releasing capability. Non-Hb-derived DAMPs such as ATP, interleukin-33, heat shock protein 70, as well as RBC membrane-derived microparticles might also contribute to the innate immune response triggered by hemolysis/hemorrhage.In this chapter we will discuss the inflammatory properties of RBC-derived DAMPs with a particular focus on Hb derivatives, as well as therapeutic potential of the endogenous Hb and heme-binding proteins haptoglobin and hemopexin in the prevention of hemolysis/hemorrhage-associated inflammation.

Although viral vectors comprise the majority of gene delivery vectors, their various safety, production, and other practical concerns have left a research gap to be addressed. The non-viral vector space encompasses a growing variety of physical and chemical methods capable of gene delivery into the nuclei of target cells. Major physical methods described in this chapter are microinjection, electroporation, and ballistic injection, magnetofection, sonoporation, optical transfection, and localized hyperthermia. Major chemical methods described in this chapter are lipofection, polyfection, gold complexation, and carbon-based methods. Combination approaches to improve transfection efficiency or reduce immunological response have shown great promise in expanding the scope of non-viral gene delivery.

The interaction between intracellular bacterial pathogens with the host immune response can result in multiple outcomes that range from asymptomatic clearance to the establishment of infection. At its core, these interactions result in multiple metabolic adaptations of both the pathogen and its host cell. There is growing evidence that the host metabolic response plays a key role in the development of immune responses against the invading pathogen. However, successful intracellular pathogens have developed multiple mechanisms to circumvent the host response to thrive in the intracellular compartment. Here, we provide a brief overview on the crucial role of fundamental metabolic host responses in the generation of protective immunity to intracellular bacterial pathogens and discuss some of the mechanisms used by these pathogens to exploit the host metabolic response to their own advantage. This understanding will further our knowledge in host-pathogen interactions and may provide new insights for the development of novel therapies.

Diet plays a fundamental role in the nutritional status, in the homeostasis and in the capacity of an individual to adapt to the environment. A proper or an inadequate nutrition has an impact on the persistence, remission and incidence of various conditions, including the infectious diseases. Consequently, nutrition has a crucial importance on survival rates and health recovery of individuals or even populations around the globe. The synergistic relationship between nutritional needs and infectious processes has been demonstrated conclusively in diverse studies. This chapter will discuss the most important nutrients, their most common natural dietary sources, the different digestive processes for each one as well as the absorption, transport, storage, excretion and function of each of the nutrients within the organism. We also go through some concepts on the interaction between nutrition and the immune system, as well as examples on the influence of nutrition or specific nutrients on some infectious diseases, and their influence on the gene expression.

Microbes have developed a series of strategies to overcome the defense mechanisms of the infected host. During pathogen-host coevolution, they develop strategy to manipulate cellular machinery particularly in subverting mitochondrion function. Mitochondria are highly dynamic organelles that constantly remodel their structure. In particular, shaping and cellular distribution of the mitochondrial network is maintained in large part by the conserved activities of mitochondrial division, fusion, motility, and tethering. Mitochondria have been long recognized for their role in providing energy production, calcium metabolism, and apoptosis. More recently, mitochondria have been also shown to serve as a platform for innate immune response. In this context, mitochondrial dynamics and shaping is not only essential to maintain cristae structure and bioenergetic to fuel cellular demands but contribute to regulate cellular function such as innate immune response and mitochondrial permeabilization. Due to their key role in cell survival, mitochondria represent attractive targets for pathogens. Therefore, microbes by manipulating mitochondrial dynamics may escape to host cellular control. Herein, we describe how mitochondrial bioenergetics, dynamics, and shaping are impacted during microbe infections and how this interplay benefits to pathogens contributing to the diseases.

Inflammasomes are large innate cytoplasmic complexes that play a major role in promoting inflammation in the lung in response to a range of environmental and infectious stimuli. Inflammasomes are critical for driving acute innate immune responses that resolve infection and maintain tissue homeostasis. However, dysregulated or excessive inflammasome activation can be detrimental. Here, we discuss the plethora of recent data from clinical studies and small animal disease models that implicate excessive inflammasome responses in the pathogenesis of a number of acute and chronic respiratory inflammatory diseases. Understanding of the role of inflammasomes in lung disease is of great therapeutic interest.

Neuroinflammation is a common pathological feature in almost all neurological diseases and is a response triggered as a consequence of the chronic activation of the innate immune response in the CNS against a variety of stimuli, including infection, traumatic brain injury, toxic metabolites, aggregated proteins, or autoimmunity. Crucial mediators of this neurinflammatory process are the intracellular protein complexes known as inflammasomes which can be triggered by pathogens as well as pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). However, chronic inflammasome activation can eventually result in cellular death and tissue damage, leading to the release of DAMPs that can reactivate the inflammasome, thereby propagating a vicious cycle of inflammation. The primary cells involved in CNS inflammasome activation are the immunocompetent microglia and the infiltrating macrophages into the CNS. However, astrocytes and neurons also express inflammasomes, and the understanding of how they are engaged in the pathogenesis of a variety of neurological diseases is crucial to develop effective therapeutic approaches for CNS pathologies that are propagated by chronic inflammasome activation. This chapter covers the activation mechanisms of relevant inflammasomes in the brain and summarizes their roles in the pathogenesis and progression of different neurological conditions.