Cytokines in health and disease

Cytokines are cellular regulators of non-immunoglobulin character. The studies of interferon, a representative cytokine, support the view that cytokines are information molecules forming a network in the animal organism. Their main task is to protect the homeostasis of the organism. This may be disturbed both by external and internal causes. The results of the studies of interferon appearing in patients with systems lupus erythematosus do not support the assumption that interferons of this type may play a role in aetiology of autoimmune diseases.     

Semaphorins in health and disease

Cell-cell communication is pivotal to guide embryo development, as well as to maintain adult tissues homeostasis and control immune response. Among extracellular factors responsible for this function, are the Semaphorins, a broad family of around 20 different molecular cues conserved in evolution and widely expressed in all tissues. The signaling cascades initiated by semaphorins depend on a family of conserved receptors, called Plexins, and on several additional molecules found in the receptor complexes. Moreover, multiple intracellular pathways have been described to act downstream of semaphorins, highlighting significant diversity in the signaling cascades controlled by this family. Notably, semaphorin expression is altered in many human diseases, such as immunopathologies, neurodegenerative diseases and cancer. This underscores the importance of semaphorins as regulatory factors in the tissue microenvironment and has prompted growing interest for assessing their potential relevance in medicine. This review article surveys the main contexts in which semaphorins have been found to regulate developing and healthy adult tissues, and the signaling cascades implicated in these functions. Vis a vis, we will highlight the main pathological processes in which semaphorins are thought to have a role thereof.     

Chemokines in health and disease

Chemokines and their receptors play a key role in development and homeostasis as well as in the pathogenesis of tumors and autoimmune diseases. Chemokines are involved in the implantation of the early conceptus, the migration of subsets of cells during embryonic development, and the overall growth of the embryo. Chemokines also have an important role in the development and maintenance of innate and adaptive immunity. In addition, they play a significant role in wound healing and angiogenesis. When the physiological role of chemokines is subverted or chronically amplified, disease often follows. Chemokines are involved in the pathobiology of chronic inflammation, tumorigenesis and metastasis, as well as autoimmune diseases. This article reviews the role of chemokines and their receptors in normal and disease processes and the potential for using chemokine antagonists for appropriate targeted therapy.     

S-nitrosylation in health and disease

S-nitrosylation is a ubiquitous redox-related modification of cysteine thiol by nitric oxide (NO), which transduces NO bioactivity. Accumulating evidence suggests that the products of S-nitrosylation, S-nitrosothiols (SNOs), play key roles in human health and disease. In this review, we focus on the reaction mechanisms underlying the biological responses mediated by SNOs. We emphasize reactions that can be identified with complex (patho)physiological responses, and that best rationalize the observed increase or decrease in specific classes of SNOs across a spectrum of disease states. Thus, changes in the levels of various SNOs depend on specific defects in both enzymatic and non-enzymatic mechanisms of nitrosothiol formation, processing and degradation. An understanding of these mechanisms is crucial for the development of an integrated model of NO biology, and for effective treatment of diseases associated with dysregulation of NO homeostasis.     

Oxytocin in health and disease

Oxytocin is a nonapeptide of the neurohypophyseal protein family that binds specifically to the oxytocin receptor to produce a multitude of central and peripheral physiological responses. Within the central nervous system oxytocin is expressed by the neurons of the hypothalamus that project into higher brain centres and the posterior pituitary gland, from where it enters the circulation by release into the portal capillaries. Centrally, it modulates, maternal, sexual, social and stress related behaviour. Peripheral actions of oxytocin are commonly associated with smooth muscle contraction, particularly within the female and male reproductive tracts. Local synthesis of oxytocin along with its receptor in these regions indicates the presence of local oxytocinergic systems. More sinister implications for oxytocin in autism, depression and several cancers have recently been identified. A greater understanding of the role of oxytocinergic mechanisms will determine the potential for targeting this regulatory peptide in the pharmacological management of these disorders.     

Microchimerism in health and disease

Microchimerism has been defined by the presence of a low number of circulating cells transferred from one individual to another. This transfer takes place naturally during pregnancy, between mother and fetus and/or between fetuses in multi-gestational pregnancies. Furthermore, the establishment of microchimerism can also occur during blood transfusion and organ transplants. Microchimeric cells have been implicated in health and disease. Microchimerism has been correlated with the hyporesponsiveness of the maternal immune system towards the fetal allograft and with the longevity of organ transplants. However, maternal microchimeric cells have been implicated in diseases of the neonate including neonatal graft-versus-host disease, severe combined immunodeficiency and erythema toxicum neonatorum. And more recently, microchimeric cells have been implicated in the pathogenesis of autoimmune diseases including systemic sclerosis and myositis.     

Angiogenesis in health and disease

Blood vessels constitute the first organ in the embryo and form the largest network in our body but, sadly, are also often deadly. When dysregulated, the formation of new blood vessels contributes to numerous malignant, ischemic, inflammatory, infectious and immune disorders. Molecular insights into these processes are being generated at a rapidly increasing pace, offering new therapeutic opportunities that are currently being evaluated.     

Aquaporins in health and disease

The molecular basis of membrane water-permeability remained elusive until the recent discovery of the aquaporin water-channel proteins. The fundamental importance of these proteins is suggested by their conservation from bacteria through plants to mammals. Ten mammalian aquaporins have thus far been identified, each with a distinct distribution. In the kidney, lung, eye and brain, multiple water-channel homologs are expressed, providing a network for water transport in those locations. It is increasingly clear that alterations in aquaporin expression or function can be rate-limiting for water transport across certain membranes. Aquaporins are likely to prove central to the pathophysiology of a variety of clinical conditions from diabetes insipidus to various forms of edema and, ultimately, they could be a target for therapy in diseases of altered water homeostasis.     

Leukotrienes in health and disease

The leukotrienes (LTs) are 5-lipoxygenase metabolites of arachidonic acid. The synthesis and release of LTs have been demonstrated in many cells and organs, and LTs are considered to be normal products of continuous metabolism of arachidonic acid. However, although evidence in favor of a critical role for LTs in regulation of physiological functions is still scarce, a growing body of evidence suggests a role for LTs in mediation of several pathophysiological processes such as generalized or local immune reactions, inflammation, asthma, shock, and trauma. LTs have been shown to have potent actions on many essential organs and systems, including the cardiovascular system (heart, blood vessels, microcirculation), the pulmonary system (lung, airways), the central nervous system (neural, glial, and vascular elements), the gastrointestinal tract, and the immune system. In these organs the effects of LTs are mediated by specific LT receptors. Identification of LTs and characterization of their regional and systemic pathological effects, together with characterization of their receptors and elucidation of their structure-activity relationships, are fundamental to developing LT antagonists or synthesis inhibitors that might prevent or reverse LT-dependent reactions. Preliminary reports have already shown that such pharmacological agents ameliorate some aspects of disease processes in experimental animals as well as in humans. In this brief review we intend to highlight the evidence that implicates LTs in normal physiological functions as well as in disease processes.     

Elastic fibres in health and disease

Elastic fibres are a major class of extracellular matrix fibres that are abundant in dynamic connective tissues such as arteries, lungs, skin and ligaments. Their structural role is to endow tissues with elastic recoil and resilience. They also act as an important adhesion template for cells, and they regulate growth factor availability. Mutations in major structural components of elastic fibres, especially elastin, fibrillins and fibulin-5, cause severe, often life-threatening, heritable connective tissue diseases such as Marfan syndrome, supravalvular aortic stenosis and cutis laxa. Elastic-fibre function is also frequently compromised in damaged or aged elastic tissues. The ability to regenerate or engineer elastic fibres and tissues remains a significant challenge, requiring improved understanding of the molecular and cellular basis of elastic-fibre biology and pathology, and ability to regulate the spatiotemporal expression and assembly of its molecular components.     

Adipose tissue in health and disease

Adipose, or fat, tissue (AT) was once considered an inert tissue that primarily existed to store lipids, and was not historically recognized as an important organ in the regulation and maintenance of health. With the rise of obesity and more rigorous research, AT is now recognized as a highly complex metabolic organ involved in a host of important physiological functions, including glucose homeostasis and a multitude of endocrine capabilities. AT dysfunction has been implicated in several disease states, most notably obesity, metabolic syndrome and type 2 diabetes. The study of AT has provided useful insight in developing strategies to combat these highly prevalent metabolic diseases. This review highlights the major functions of adipose tissue and the consequences that can occur when disruption of these functions leads to systemic metabolic dysfunction.     

Sleep mechanisms in health and disease

Excess sleepiness, abnormal sleep patterns, non-restorative sleep, and fatigue are becoming increasingly pervasive in modern society. Identifying substances and mechanisms that modulate sleep and vigilance during health and disease is a critical prelude to eventual development of interventions to prevent or alleviate these disabling problems. A unified interdisciplinary approach that includes neurophysiology, neuroanatomy, neurochemistry, and molecular biology will promote elucidation of the complex biology of sleep. Integration of basic sleep physiology with modern genetic techniques will eventually lead to identification of specific genes and substances involved in regulation of various facets of sleep. The review presented here highlights recent progress in defining the anatomy and physiology of sleep-wake regulatory systems, delineating the role of homeostatic and circadian process in regulating sleep and wakefulness, and establishing the relationship of sleep and sleep disorders to other medical conditions. Particular emphasis is placed on reviewing the interactions between sleep, infectious challenge, and host defense response, and on identifying mechanisms that contribute to variation in sleep patterns among various strains of inbred mice.