Biochemist India: What role do cytokines play in autoimmune diseases?

Wednesday, November 2, 2011

What role do cytokines play in autoimmune diseases?

biochemist INDIA (2 Nov 2011): Cytokines, a varied group of signalling chemicals in the body, have been described as the software that runs the immune system, but when that software malfunctions, dysregulation of the immune system can result in debilitating autoimmune diseases.

In the introductory Editorial, researchers identifies cytokines as the first step in the onset of immune responses in which the body attacks its own cells and tissues, leading to the development of autoimmune diseases. Drs Moudgil and Choubey present an overview of the role cytokines play in the induction, regulation, and treatment of autoimmunity. An original research article, ‘Critical Cytokine Pathways to Cardiac Inflammation’, by Noel Rose, The Johns Hopkins Schools of Medicine and Public Health (Baltimore, MD), describes a mouse model of autoimmune myocarditis – inflammation of the heart muscles – that is triggered by infection with Coxsackievirus B3. The model allows researchers to study the cytokine pathways involved in this disease, with the goal of identifying chemical markers that could be used to predict patients more likely to experience an autoimmune reaction after infection.

most up-to-date findings and unique perspectives on the role of cytokines in autoimmune diseases are published in a special issue of Journal of Interferon & Cytokine Research; available free online for a limited time.

No comments:

Post a Comment

Lipid of the week : Sphingomyelin

Not merely membrane building blocks, sphingomyelin species carry out important signaling roles as precursor molecules and by providing localized platforms.

Sphingomyelin species comprise a ceramide unit and a phosphorylcholine or phosphoethanolamine polar headgroup. Typically, sphingosine is the long-chain base component of ceramide, although other long-chain bases can be present; differences in the sphingoid base and the fatty acid components (which are very-long-chain saturated and monounsaturated) confer great variability on the composition of sphingomyelins¹.

As a major constituent of cell membranes, sphingomyelin is found at particularly high concentrations in the membranes of nerve cells (in the myelin sheaths) and red blood cells. It was previously thought to have a purely structural role, similar to the function of phosphatidylcholine, through intermolecular interactions mediated by the 2-amide group, the 3-hydroxy group and the 4,5-trans double bond of the sphingoid base. However, it is now appreciated that sphingomyelin has a high affinity for cholesterol and that these two lipids pack tightly into liquid-ordered domains among a liquid-disordered phase to form lipid rafts¹². These membrane microdomains are thought to function as signaling platforms that regulate the localization and interactions of proteins. But sphingomyelin does not just influence signaling as a component of lipid rafts — it is also a precursor to ceramides and other sphingolipid metabolites that comprise the sphingomyelin cycle or sphingolipid network.

Sphingomyelin biosynthesis begins in the Golgi but continues in the plasma membrane. Sphingomyelin synthase catalyzes the transfer of phosphorylcholine from phosphatidylcholine to ceramide. The consequent decrease in ceramide levels is accompanied by an increase in the levels of sphingomyelin and the release of the well-known signaling molecule diacylglycerol. Alternatively, ceramide can also first be converted to ethanolamine phosphorylceramide through the transfer of the head group from phosphatidylethanolamine followed by sequential methylation of the ethanolamine moiety to a choline group, although whether this pathway is physiologically relevant is unknown¹.

Conversely, sphingomyelin can be metabolized to ceramide (and further, to other biologically active sphingolipids such as sphingosine and sphingosine-1-phosphate) by sphingomyelinases. The function of ceramide as a proapoptotic molecule is well known, although the exact mechanism through which this lipid induces cell death is not fully understood. By contrast, a decrease in ceramide levels accompanies the accumulation of sphingomyelin in cells of the brain, spleen and liver that occurs as a consequence of a deficiency in sphingomyelinase in Niemann–Pick disease types A and B¹. Notably, levels of cholesterol are also elevated in Niemann–Pick disease, which is consistent with reports suggesting that the metabolism, as well as the distribution, of these two lipids is linked, which has clear implications for several other diseases.

Pages

Wednesday, November 2, 2011

What role do cytokines play in autoimmune diseases?

No comments:

Post a Comment