Liver X Receptors (LXRs), composed of LXR[alpha] and LXR[beta], are ligand activated nuclear receptors that are important regulators of cholesterol and lipid metabolism. LXRs control expression of genes involved in cholesterol efflux, fatty acid metabolism, and inflammation in tissues such as the liver and intestine. LXR[alpha] is highly expressed in liver resident macrophages, called Kupffer cells, which are involved in clearing pathogens from the portal circulation, as well as sensing tissue injury. During liver disease, such as nonalcoholic steatohepatitis (NASH), Kupffer cells are responsible for initiating a proinflammatory response program; therefore, I sought to understand the LXR-dependent responses modulating cholesterol accumulation and inflammation in Kupffer cells at both the steady state and during disease. I found a decreased expression of cholesterol efflux and inflammatory genes in Kupffer cells of mice lacking LXRs throughout all tissues but aimed to understand the function of LXRs intrinsic to Kupffer cells. Therefore, I studied a Lyz2 Cre and a novel Clec4f Kupffer cell specific Cre mouse lacking LXRs and saw an expansion of a new F4/80HiCd11bIntTim4Neg Kupffer cell population that is associated with fatty liver disease. Consequently, LXR activation may have beneficial properties, so pharmacological activation with a synthetic mimetic of the natural LXR ligand desmosterol was analyzed. Results suggest that this desmosterol mimetic dampens hepatic inflammation, lipid accumulation, and fibrosis, and may not only be targeting the liver, but also altering gene expression in the intestine as well. Thus, pharmacological activation of LXRs may act therapeutically in patients with fatty liver disease.

Monocytes represent one of the major types of white blood cells in man which prevent infection by ingesting and killing invading pathogens and by releasing factors which stimulate and regulate lymphocytes. Monocytes "purify" the blood, removing immune complexes, mediating inflammatory responses, and initiating tissue repair. Human Monocytes represents an up-to-date, definitive account of this important cell. It covers the cells biochemical, immunological, and inflammatory functionsand its role in many diseases, including asthma, atherosclerosis, rheumatoid arthritis, and AIDS.

Myelomonocytes are the multipotent cells in the stage of blood cell differentiation, which mainly comprise blood monocytes, tissue macrophages and subset of dendritic cells. Actually, their position and ability of judgement of the health of tissue or organ environment are the key initiators of tissue-specific immune response in a local and global fashion. Interestingly, the morpho-functional aspects of this group of cells vary to a wide range with their positional diversity. Their ability to communicate or represent the tissue microenvironment to the peripheral immune system and efficiency to engage the system to effector activation hold the key for a successful immune endeavour. The present volume shows some glimpses of such an extensive area of current immunology research.

Stellate Cells in Health and Disease is a comprehensive reference providing the most up-to-date knowledge and perspectives on the function of stellate cells affecting the liver and other organs. The text presents comprehensive coverage of their already established role in hepatic fibrosis along with the newer emerging evidence for stellate cell participation in the liver cell (hepatocyte) survival and regeneration, hepatic immunobiology, transplant tolerance, and liver cancer. Chapters describe both animal and human research and the relevance of findings from animal research to human pathophysiology, and also contain sections on future directions which will be of special interest to basic and clinical researchers working on liver fibrosis, hepatic biology, and pathobiology. Presents coverage of the mechanisms of liver fibrosis with stellate cells as a target for therapy. Shows stellate cells as a major participant in hepatic immunobiology, including transplantation immunology. Key illustrations show the phenotypical changes in stellate cells in situ and tissue culture, their interactions with other cell types, signaling pathways and demonstrate the functions and roles of stellate cell in pathological processes.

This book focusses on the latest results related to the field of bile acids as signaling molecules and describes how these receptors have become a major pharmacological target. It covers all major areas of research in this field, from genetics, chemistry, in silico modeling, molecular biology to clinical applications, offering a cross-country view of the functional role of bile acids as signaling molecules, virtually acting on all major areas of metabolism. While FXR and GPBAR1 are essential bile acid sensors that integrate the de novo bile acid synthesis with intestinal microbiota and liver metabolism, in a broader sense, BARs play a pathogenic role in the development of common human alignments including liver, intestinal and metabolic disorders, such as steatosis (NAFLD) and steato-hepatitis (NASH), diabetes, obesity and atherosclerosis.

Liver disease in children is increasing in prevalence, placing a huge burden on healthcare systems and often requiring long-term management. Offering an integrative approach to the science and clinical practice of pediatric hepatology, this is the definitive reference text for improved diagnosis and treatment strategies. In the new edition of this authoritative text, chapters have been thoroughly revised in line with major advances in the field, such as recognizing the increased frequency of fatty liver disease, and how genetic testing has the potential to establish earlier diagnoses for a variety of diseases. Disorders covered include cholestasis, metabolic disorders and hepatitis, with their presentation across the spectrum of infancy, childhood and adolescence discussed. The indications and surgical aspects of liver transplant are explained and post-transplant care is described in detail. This is a valuable resource for pediatricians, hepatologists, gastroenterologists and all clinicians involved in the care of children with liver diseases.

The liver is an exceptionally complex and diverse organ that functions both as an exocrine and an endocrine gland. It secretes bile, which contains many con stituents in addition to bile salts, and it synthesizes and releases many substances in response to the body's demands, including prohormones, albumin, clotting factors, glucose, fatty acids, and various lipoproteins. It has a dual blood supply providing a rich mixture of nutrients and other absorbed substances via the portal vein and oxygen-rich blood via the hepatic artery. This functional heterogeneity is accompanied by cellular heterogeneity. The liver contains many cell types including hepatic parachymal cells, Kiipffer cells, Ito cells, and endothelial cells. The most abundant cell type, the parenchymal cells, are biochemically and structurally heterogeneous. The cells in the oxygen-rich areas of the portal triad appear more dependent on oxidative metabolism, whereas those around the central vein (pericentral, perivenous, or centrolobular areas) are more dependent upon an anaerobic mechanism. Throughout this volume the latter three terms are used synonymously by various authors to indicate the five to eight layers of cells radiating from the central vein. Structural and metabolic heterogeneity of hepatic parenchymal cells has been demonstrated by a variety of approaches, including histochemical, ultra structural, and ultramicrobiochemical studies. This microheterogeneity is linked to the physiological functions of the liver and its response to injurious substances.