Current Drug Targets - Inflammation & Allergy 

About: Current Drug Targets - Inflammation & Allergy is an academic journal. The journal publishes majorly in the area(s): Inflammation & Chemokine. It has an ISSN identifier of 1568-010X. Over the lifetime, 203 publications have been published receiving 12323 citations.

Macrophages in inflammation.

Abstract: The inflammatory process is usually tightly regulated, involving both signals that initiate and maintain inflammation and signals that shut the process down. An imbalance between the two signals leaves inflammation unchecked, resulting in cellular and tissue damage. Macrophages are a major component of the mononuclear phagocyte system that consists of closely related cells of bone marrow origin, including blood monocytes, and tissue macrophages. From the blood, monocytes migrate into various tissues and transform macrophages. In inflammation, macrophages have three major function; antigen presentation, phagocytosis, and immunomodulation through production of various cytokines and growth factors. Macrophages play a critical role in the initiation, maintenance, and resolution of inflammation. They are activated and deactivated in the inflammatory process. Activation signals include cytokines (interferon gamma, granulocyte-monocyte colony stimulating factor, and tumor necrosis factor alpha), bacterial lipopolysaccharide, extracellular matrix proteins, and other chemical mediators. Inhibition of inflammation by removal or deactivation of mediators and inflammatory effector cells permits the host to repair damages tissues. Activated macrophages are deactivated by anti-inflammatory cytokines (interleukin 10 and transforming growth factor beta) and cytokine antagonists that are mainly produced by macrophages. Macrophages participate in the autoregulatory loop in the inflammatory process. Because macrophages produce a wide range of biologically active molecules participated in both beneficial and detrimental outcomes in inflammation, therapeutic interventions targeted macrophages and their products may open new avenues for controlling inflammatory diseases.

Nitric oxide production and signaling in inflammation.

Abstract: Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. It possesses cytotoxic properties that are aimed against pathogenic microbes, but it can also have damaging effects on host tissues. NO reacts with soluble guanylate cyclase to form cyclic guanosine monophosphate (cGMP), which mediates many of the effects of NO. NO can also interact with molecular oxygen and superoxide anion to produce reactive nitrogen species that can modify various cellular functions. These indirect effects of NO have a significant role in inflammation, where NO is produced in high amounts by inducible nitric oxide synthase (iNOS) and reactive oxygen species are synthesized by activated inflammatory cells. The present review deals with NO production and signaling in inflammation, especially in relation to human neutrophils and eosinophils.

Epidemiology of psoriasis.

Abstract: The prevalence of psoriasis is relatively high in the general population, ranging between 0.6% and 4.8%, mainly as a result of chronicity and the absence of a cure. Although genetic-environmental interaction has been proposed as a model for the causation of psoriasis, the evidence for environmental factors is rather scarce. Risk factors, which have been documented in epidemiological studies include smoking, alcohol consumption, diet, infection, drugs, and stressful life events. Psoriasis affects the quality of life to substantial degree. Apart from a few cross-sectional surveys of large series of psoriatic patients, there have been no formal studies of the natural history and prognosis of established psoriasis. By imposing methodologic control and a numerate approach, epidemiology can offer a major contribution to understand psoriasis.

Osteoblasts and Osteoclasts in Bone Remodeling and Inflammation

Abstract: Bone homeostasis is maintained by a balance between bone resorption by osteoclasts and bone formation by osteoblasts. Osteoblasts not only play a central role in bone formation by synthesizing multiple bone matrix proteins, but regulate osteoclast maturation by soluble factors and cognate interaction, resulting in bone resorption. Osteoclast maturation requires stimulation by RANKL expressed on osteoblasts, and the cognate interaction is mediated by firm adhesion via ICAM-1. During the processes, pro-inflammatory cytokines such as IL-1 and TNF-alpha, cause an imbalance in bone metabolism, by favoring bone resorption via the induction of RANKL and ICAM-1 on osteoblasts. These inflammatory signals originate from the immune system, the largest source of cell-derived regulatory signals, and such immunological signals to the bone are transmitted primarily via osteoblasts to induce osteoclast maturation, resulting in secondary osteoporosis. Actually, such phenomena mainly occur at the interface between proliferating synovium and bone tissue in rheumatoid arthritis (RA). Thus, therapeutic strategies for these conditions, an anti-TNF-alpha antibody and an IL-1 receptor antagonist, effective for treating RA disease activity, also reduce secondary osteoporosis and joint destruction. Based on an improved understanding of immune signals, investigation of the suppression of cell functions may lead to improved understanding and better treatment of diseases of bone metabolism and osteoporosis.

Role of inflammatory mediators in angiogenesis.

Abstract: The angiogenic process involves several cell types and mediators, which interact to establish a specific microenvironment suitable for the formation of new capillaries from pre-existing vessels. Angiogenesis occurs in several physiological and pathological conditions, such as embryo development and wound healing, diabetic retinopathy and tumours. Inflammatory cells, namely monocytes/macrophages, T lymphocytes and neutrophils, fully participate in the angiogenic process by secreting cytokines that may affect endothelial cell (EC) functions, including EC proliferation, migration and activation. Angiogenesis is the result of a net balance between the activities exerted by positive and negative regulators. With regards to inflammatory cells and endothelium cross-talk, such balance is conceptually very similar to that of pro-inflammatory and anti-inflammatory mediators that modulate an appropriate inflammatory response. In this review we will mainly discuss the relevance of both physiological and pathological inflammatory processes in angiogenesis, with particular regards to microenvironmental contribution. We will also describe some of the most relevant pro-inflammatory cytokines in the modulation of the angiogenic process. Furthermore, we will concentrate on what has been recently reported about the mechanism by which some of these cytokines are induced during inflammation to promote a suitable microenvironment for angiogenesis and tumour progression. Pro-angiogenic cytokines, such as IL-1 and TNF, and anti-angiogenic cytokines such as IFN-gamma and IL-12, will be briefly described. We will try to provide a rationale for the use of both cytokines and cytokine blockades as novel potential pharmaceutical targets to modulate angiogenesis in chronic inflammation as well as in cancer.