The cytokine MIF (Macrophage Migration Inhibitory Factor) is an integral mediator of the innate immune system. Monocytes and macrophages constitutively express large amounts of MIF, which is rapidly released after exposure to bacterial toxins and cytokines. MIF exerts potent proinflammatory activities and is an important cytokine of septic shock. MIF regulates innate immune responses to endotoxin and gram-negative bacteria by modulating the expression of TLR4 (Toll-Like Receptor-4), the signal-transducing molecule of the LPS (Lipopolysaccharide) receptor complex (Ref.1). Cells may take up MIF by endocytosis — a process by which a cell's outer membrane engulfs extracellular substances (often in a nonspecific way) and imports them into the cell in[..]

Blood vessel growth and stability are under the exquisite control of a network of pro- and anti-angiogenic factors. Disruption of the balance between these factors is a characteristic of tumor growth and many vascular diseases. Endogenous angiogenesis inhibitors, particularly those that act broadly at the earliest stages, are excellent pharmacological tools in combating pathogenic vessel growth. PEDF (Pigment Epithelium Derived Factor) is a potent and broadly acting neurotrophic factor that promotes survival of neurons in many regions of the CNS (Central Nervous System) from degeneration caused by serum withdrawal or glutamate cytotoxicity and oxidative damage. Glutamate neurotoxicity involves an increase in intracellular calcium resulting from the opening of NMDA[..]

Various lipid molecules serve as second messengers for transducing signals from the cell surface to the cell interior and trigger specific cellular responses. Sphingolipids represent a complex group of lipids that have recently emerged as new transducers in eukaryotic cells. Sphingolipids are found in all mammalian cells and are mostly located in the plasma membrane. They all contain as a backbone a long-chain base – the sphingoid base (mostly sphingosine) – linked to a fatty acid by an amide bond, thus forming ceramide. Addition of a phosphocholine substituent or sugar to ceramide gives rise to the major sphingolipid SM (sphingomyelin) or to glycosphingolipids, respectively. Ceramide is also produced by breakdown of all sphingolipids by glycosidases (for[..]

Various lipid molecules serve as second messengers for transducing signals from the cell surface to the cell interior and trigger specific cellular responses. Recently, several sphingolipids have emerged as cellular constituents that are able to promote, mediate or counterbalance apoptosis. Sphingolipids are a family of membrane lipids whose structure is made up of a long-chain sphingoid base backbone (such as sphingosine), an amide-linked fatty acid of varying chain and one of various polar head groups (hydroxyl for ceramide, phosphorylcholine for sphingomyelin, and carbohydrate residues for glycosphingolipids). Addition of a phosphocholine substituent or sugar to ceramide gives rise to the major sphingolipid SM (sphingomyelin) or to glycosphingolipids. Ceramide is[..]

The sphingolipids are primarily situated in the noncytoplasmic leaflet of cellular membranes contribute to the structural integrity and fluidity characteristics of cell membranes and signal transduction complexes. Ceramide sits at the hub of sphingolipid metabolism as the neutral, lipid building block for complex sphingolipids and glycosphingolipids, serving as a substrate for more than 11 different enzymes Ceramide is also a key intermediate for the biosynthesis of the major plasma membrane sphingolipids like  Sphingomyelin(SM) and Glycosphingolipids (GSLs). Ceramides typically induces growth arrest and apoptosis, whereas S1P promotes cell proliferation and survival. Other sphingolipids such as sphingosine and sphinganine also function as pro-apoptotic factors.[..]

Sphingosine-1-phosphate (S1P) is a bioactive sphingomyelin derivative that is present in plasma and serum at high nanomolar concentrations. S1P acts via the specific cell surface G-protein-coupled receptors, S1P1-5. S1P1 and S1P2 were originally identified from vascular endothelial cells (ECs) and smooth muscle cells, respectively. S1P receptors modulate multiple intracellular pathways and thereby regulate central cellular processes, such as survival, proliferation and cytoskeletal organization. S1P, which directly acts on ECs, is involved in the regulation of angiogenesis and mural cell recruitment during development and in the adult.  Vascular endothelial cell growth factors (VEGFs), on the othe hand, are recognized as the most crucial driver of vasculogenesis[..]

The experience of pain in response to noxious stimuli serves a crucial biological purpose: it alerts a living organism to environmental dangers, inducing behavioral responses that protect the organism from further damage. In contrast, chronic pain arising from disease states and/or pathological functioning of the nervous system offers no advantage and may be debilitating to those afflicted. Control and treatment of chronic pain remain major clinical challenges. The calcium-sensing protein DREAM (Downstream Regulatory Element Antagonistic Modulator) is a putative transcriptional repressor involved in modulating pain (Ref.1).DREAM is constitutively expressed in certain neurons and transcriptional activity of the repressor DREAM depends on its high affinity binding to a[..]

Helicobacter pylori is a gram negative bacterium that causes chronic inflammation in essentially all hosts, a process that increases the risk of developing peptic ulceration, distal gastric adenocarcinoma, and gastric mucosal lymphoproliferative disease. This bacterium also is the most common cause of ulcers worldwide. H. pylori infection is most likely acquired by ingesting contaminated food and water and through person to person contact. The infection is more common in crowded living conditions with poor sanitation. Infected individuals usually carry the infection indefinitely unless they are treated with medications to eradicate the bacterium. One out of every six patients with H. pylori infection develops ulcers of the duodenum or stomach. H. pylori are also[..]

The macrophage differentiation system in mouse establishes the fact that, the macrophages stop proliferate during the process of cell differentiation. Induction of METS (Mitogenic Ets Transcriptional Suppressor METS) otherwise known as Ets (E26 Avian Leukemia Oncogene) repressor, leads to terminal differentiation and cell cycle arrest. Inside macrophages, METS blocks HRas1 (Harvey Rat Sarcoma Virus Oncogene-1)-dependent proliferation without inhibiting HRas1-dependent expression of cell type-specific genes by selectively replacing Ets activators on the promoters of cell cycle control genes. Anti-proliferative effects of METS require its interaction with Ddx20 (DEAD (Asp-Glu-Ala-Asp) Box Polypeptide-20) that assembles a novel co-repressor complex (Ref.1 and 2). The[..]

MSP (Macrophage-Stimulating Protein) also known as HGFL (Hepatocyte Growth Factor–Like Protein,) is a plasminogen-like growth factor that mediates its biological activities by activating the receptor tyrosine kinase RON  also known as MSTR1, (Macrophage Stimulating Receptor-1), a member of the MET proto-oncogene family . The alpha-chain of MSP consists of an N-terminal PAN module followed by four kringle domains and is disulfide linked to the trypsin-like beta-chain. This protein is secreted as an inactive single-chain precursor pro-MSP, which requires proteolytic cleavage at the Ser-Lys-Leu-Arg483, Val484 bond to attain functional activity. MSP is constitutively expressed by hepatic parenchymal cells, as well as in lungs, adrenal glands, placenta,[..]

Immune and inflammatory responses are rightly regulated to maintain a homoeostatic balance between an effective immune response and tissue damage to the host. Nitric Oxide is the principal mediator of many of the cytokine-inducible macrophage activities during a normal cell-mediated immune response. STK (Stem Cell-Derived Tyrosine Kinase), the murine homolog of the human RON (RON Protein Tyrosine Kinase/ Receptor d’origine nantais), is expressed on murine resident peritoneal macrophages. The ligand for STK, MSP (Macrophage Stimulating Protein), is a serum protein that is activated by members of the Coagulation Cascade (Tissue Clotting Factors) in response to tissue damage. MSP has an inhibitory effect on the production of Nitric Oxide by activated peritoneal[..]

Malaria is the world's largest parasitic disease, killing more people than any other communicable disease except Tuberculosis. Malaria is a major public health problem in more than 100 countries, inhabited by a total of some 2.4 billion people, or close to half of the world's population. Each year, 300–500 million people contract malaria and about 3 million die, most of which are children under five years old. In absolute numbers, malaria kills 3,000 children per day under the age of five. The total number of deaths readily exceeds that from AIDS. Human malaria is caused by infection with intracellular protozoan parasites of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Four species of Plasmodium infect humans: P. falciparum, P.[..]