Phosphatidylserine-specific phospholipase A1 stimulates histamine release from rat peritoneal mast cells through production of 2-acyl-1-lysophosphatidylserine

Lysophosphatidylserine (1-acyl-2-lyso-PS) has been shown to stimulate histamine release from rat peritoneal mast cells (RPMC) triggered by FcepsilonRI (high affinity receptor for IgE) cross-linking, although the precise mechanism of lyso-PS production has been obscure. In the present study we show that phosphatidylserine-specific phospholipase A(1), PS-PLA(1), stimulates histamine release from RPMC through production of 2-acyl-1-lyso-PS in the presence of FcepsilonRI cross-linker. The potency of 2-acyl-1-lyso-PS was almost equal to that of 1-acyl-2-lyso-PS. A catalytically inactive PS-PLA(1), in which an active serine residue (Ser(166)) was replaced with an alanine residue did not show such activity. sPLA(2)-IIA, another secretory PLA(2) that is capable of producing lyso-PS in vitro, was also a poor histamine inducer against RPMC. PS-PLA(1) significantly stimulated histamine release from crude RPMC, indicating that lyso-PS is mainly derived from cells other than mast cells. In agreement with this phenomenon, the enzyme stimulated the histamine release more efficiently when RPMC were mixed with apoptotic Jurkat cells. Under these conditions, lyso-PS with unsaturated fatty acid was released from the apoptotic cells treated with PS-PLA(1). Finally, heparin, which has affinity for PS-PLA(1), completely blocked the stimulatory effect of the enzyme. In conclusion, PS-PLA(1) may bind to heparan sulfate proteoglycan, efficiently hydrolyze PS appearing on plasma membranes of apoptotic cells, and stimulate mast cell activation mediated by 2-acyl-1-lyso-PS.     

Emerging role of HMGB1 in lung diseases: friend or foe

Lung diseases remain a serious problem for public health. The immune status of the body is considered to be the main influencing factor for the progression of lung diseases. HMGB1 (high‐mobility group box 1) emerges as an important molecule of the body immune network. Accumulating data have demonstrated that HMGB1 is crucially implicated in lung diseases and acts as independent biomarker and therapeutic target for related lung diseases. This review provides an overview of updated understanding of HMGB1 structure, release styles, receptors and function. Furthermore, we discuss the potential role of HMGB1 in a variety of lung diseases. Further exploration of molecular mechanisms underlying the function of HMGB1 in lung diseases will provide novel preventive and therapeutic strategies for lung diseases.     

S100A2 in cancerogenesis: a friend or a foe?

Owing to the exceptional intracellular distribution and the heterogeneous expression pattern during transformation and metastasis in various tumors, the EF-hand calcium-binding protein S100A2 attracts increasing attention. Unlike the majority of S100 proteins, S100A2 expression is downregulated in many cancers and the loss in nuclear expression has been associated with poor prognosis. On the other hand, S100A2 is upregulated in some cancers. This mini review highlights the general characteristics of S100A2 and discusses recent findings on its putative functional implication as a suppressor or promoter in cancerogenesis.     

Airway wall remodeling: friend or foe?

Airway wall remodeling is well documented for asthmatic airways and is believed to result from chronic and/or short-term exposure to inflammatory stimuli. Airway wall remodeling can contribute to airway narrowing as well as to the airway hyperresponsiveness, which is a characteristic abnormality in asthma. However, the potential for airway narrowing could be much worse if it were not for some of the protective effects of remodeling that may help to limit airway narrowing in asthmatic patients. This minireview discusses the evidence for airway wall remodeling and its effects, friend and/or foe, on airway narrowing in asthmatic patients.     

PARG: a macrodomain in disguise

Our understanding of poly-ADP-ribosylation as a posttranslational modification was limited by the lack of structural information on poly-ADP-ribose (PAR) hydrolysing enzymes. A recent study in Nature (Slade et?al., 2011) reports the structure of PAR glycohydrolase (PARG), revealing unexpected similarity to the ubiquitous ADP-ribose-binding macrodomains.     

Calcitonin: A useful old friend

Calcitonin regulates blood calcium levels and possesses certain clinically useful anti-fracture properties. Specifically, it reduces vertebral fractures in postmenopausal osteoporotic women significantly compared to a placebo. Nevertheless, the use of calcitonin has declined over the years and salmon calcitonin is no longer the first-line treatment for many of its indications. Commercial calcitonin only exists in intranasal or injectable preparations, which are less preferable for patients. Efficacy of a potential oral formulation has been under investigation but achieving adequate bioavailability remains a conundrum and the latest phase III trials have not shown promising evidence justifying its use. Associations with cancer have also derailed this treatment option. Furthermore, the rise of bisphosphonates and, more recently, monoclonal antibodies (such as denosumab), has revolutionised the treatment of osteoporotic fractures. Therefore, we are posed with an interesting question: is calcitonin a treatment of the past? This review aims to explore the reasons behind this paradigm shift and outline the potential role of calcitonin in the management of fractures and other conditions in the years to come.     

A blessing in disguise: Transposable elements are more than parasites

Transposable elements (TEs) are various DNA fragments inserted throughout genomes, which are able to move or duplicate themselves. Recent advances in genomics have placed them back at the center of genome dynamics. One of the emerging observations, especially in plants, is the importance of interactions between TEs and genes to generate or to participate in relevant functions essential for development, adaptation and/or life cycle. A recent publication illustrates the influence of TEs epigenetic control on the expression of a neighboring gene crucial for reproduction. Different reports lately showed that a fundamental mechanism such as imprinting is likely to be closely linked to the dynamics of TEs epigenetic control. Here we discuss and bring together these and others recent findings, to underline that the cis-vicinity or the trans-relation between TEs and genes could bring unexpected but positive outcomes.     

Disease and the devil: density-dependent epidemiological processes explain historical population fluctuations in the Tasmanian devil

Australia's last mega-carnivore marsupial, the Tasmanian devil Sarcophilus harrisii , Dasyuridae is endemic to the island state of Tasmania. The recent appearance and rapid spread of a debilitating and usually lethal, cancer-like disease has raised concerns regarding the species' future. We used a demographic matrix modelling approach to evaluate the potential long-term implications of epidemics on this population. Both adult survival and temporally autocorrelated re-occurrence of disease were expressed as a function of female abundance. Large fluctuations in abundance resulted when disease outbreaks were conditioned to be density-dependent; however, this resulted in a low probability of quasi-extinction due to the dissipation of disease transmission at low densities. Epidemic stochasticity alone in an otherwise deterministic model resulted in major population cycles occurring every 77–146 yr, consistent with historical reports. Although epidemics in this species may not result in extinction directly, the contemporary presence of additional mortality sources during periods of low abundance may increase extinction risk.