Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 8, Issue 4, 2009

Members of the S100 protein family comprise a multigenic group of non-ubiquitous cytoplasmic Ca2+-binding proteins of the EF-hand type, differentially expressed in a wide variety of cell types. They are small acidic proteins (10-12 kDa) that are found exclusively in vertebrates, and have been implicated in the regulation of many diverse processes such as signal transduction, cell growth and motility, cell-cycle regulation, t Read More

S100A8 and S100A9 are two soluble calcium-binding proteins highly expressed in myeloid cells, mainly neutrophils (45% of cytosolic proteins) or monocytes (1-5%) and also early differentiated macrophages. In neutrophils, they are believed to be expressed as a 1/1 non covalent heterodimer; the process of dimer and mainly tetramer formation is calcium dependent. The S100A8/S100A9 calcium loaded complex binds arachido Read More

The calgranulins are a subgroup of proteins in the S100 family (calgranulin A, S100A8; calgranulin B, S100A9 and calgranulin C, S100A12) that provide protective anti-infective and anti-inflammatory functions for the mammalian host. In this review, we discuss the structure-function relationships whereby S100A8 and S100A9, and for comparison, S100A12, provide intra- and extracellular protection during the comple Read More

Asthma and chronic obstructive pulmonary disease (COPD) are persistent inflammatory conditions that have exhibited significantly increased prevalence in the past two decades. Though many current medications relieve the symptoms of obstructive airway disease, morbidity can still increase over time in individual patients. With particular respect to asthma, despite satisfactory control of symptoms in most patients wi Read More

The S100A8/S100A9 heterodimer, commonly referred to as calprotectin (CP), is a member of the S100 subfamily of EF-hand calcium binding proteins that is largely expressed in activated monocytes and macrophages and has well-defined functions in acute and chronic inflammation. Indeed, certain S100 proteins including S100A8/A9 are exported from cells by an as-yet unknown mechanism. Once outside the cell, S10 Read More

Human cancer is a chronic disease that originates from transformed tumor cells harboring genetic as well as epigenetic alterations. It develops via a multi-step process that can be divided both operationally and mechanistically into three phases: initiation, promotion and progression. However, cancer is not merely an autonomous mass of mutant cells, but is composed of multiple cell types, such as fibroblasts and epithelial cells, Read More

Provoked by the discovery of metastasis-inducing endogenous ligands of TLR4 that has been recognized as a sensor for extrinsic pathogens, I propose an extended concept for danger signal that originally meant sentinels over tissue destruction by cancer. The so-called “homeostatic inflammation” concept includes signals before destruction actually takes place such as those in pre-metastatic microenvironment and p Read More

The function of the exocrine pancreas is the production and secretion of digestive enzymes. Major pathologies of the exocrine pancreas are pancreatitis, a sterile inflammation, and pancreatic adenocarcinoma, a highly lethal tumor. Both diseases involve cells of the immune system and calcium binding proteins of the S100 family. Here, we review the known function of these proteins in pancreatitis and pancreas cancer. F Read More

Current vaccine research is now heavily focused on improving the efficacy and potency of sub-unit peptide vaccines. Many successful vaccines developed in past decades have been able to sufficiently prime proper immune responses without the use of any specific adjuvant immune mediators. Due to the intrinsic nature of more immune-evading pathogens and neoplasms, novel “tricks” are needed to elucidate a pro Read More

T cells specific for haptens determine immunopathology, as for the recognition of the β-lactamic ring by CD4+ T helper cells, responsible for the severe immune response to Penicillin in allergic patients. In this review we report studies that address functional and molecular aspects of hapten recognition by α/β T cells, enlightening the most relevant examples of hapten-specific T cells and their role in vivo. Using Trinitrophenyl a Read More

Glucocorticoids (GCs) represent the cornerstone of treatment of patients with bronchial asthma; however, inflammation in bronchial asthma is sometimes incompletely controlled. GCs switch on the expression of anti-inflammatory genes by binding to DNA and recruiting transcriptional coactivator molecules. In contrast, they can switch off activated inflammatory genes by recruiting transcriptional repressor molecules s Read More