Choice of Mouse Strain Influences the Outcome in a Mouse Model of Chemical-Induced Asthma

Background

The development of occupational asthma is the result of interactions between environmental factors and individual susceptibility. We assessed how our model of chemical-induced asthma is influenced by using different mouse strains.

Methodology/Principal Findings

On days 1 and 8, male mice of 7 different strains (BALB/c, BP/2, A/J, C57Bl/6, DBA/2, CBA and AKR) were dermally treated with toluene-2,4-diisocyanate (TDI) (0.3%) or vehicle (acetone/olive oil, AOO, 2∶3) on each ear (20 µl). On day 15, they received an oropharyngeal instillation of TDI (0.01%) or AOO (1∶4). Airway reactivity to methacholine, total and differential cell counts in bronchoalveolar lavage (BAL) and total serum IgE and IgG_2a levels were measured. Lymphocyte subpopulations in auricular lymph nodes and in vitro release of cytokines by ConA stimulated lymphocytes were assessed. In TDI-sensitized and challenged mice, airway hyper-reactivity was only observed in BALB/c, BP/2, A/J and AKR mice; airway inflammation was most pronounced in BALB/c mice; numbers of T-helper (CD4⁺), T-activated (CD4⁺CD25⁺), T-cytotoxic (CD8⁺) and B- lymphocytes (CD19⁺) were increased in the auricular lymph nodes of BALB/c, BP/2, A/J and CBA mice; elevated concentrations of IL-4, IL-10, IL-13 and IFN-γ were detected in supernatant of lymphocytes from BALB/c, BP/2, A/J, C57Bl/6 and CBA mice cultured with concanavaline A, along with an increase in total serum IgE.

Conclusion

The used mouse strain has considerable and variable impacts on different aspects of the asthma phenotype. The human phenotypical characteristics of chemically-induced occupational asthma were best reproduced in Th2-biased mice and in particular in BALB/c mice.     

Proteomic Alterations in B Lymphocytes of Sensitized Mice in a Model of Chemical-Induced Asthma

Introduction and Aim

The role of B-lymphocytes in chemical-induced asthma is largely unknown. Recent work demonstrated that transferring B lymphocytes from toluene diisocyanate (TDI)-sensitized mice into naïve mice, B cell KO mice and SCID mice, triggered an asthma-like response in these mice after a subsequent TDI-challenge. We applied two-dimensional difference gel electrophoresis (2D-DIGE) to describe the “sensitized signature” of B lymphocytes comparing TDI-sensitized mice with control mice.

Results

Sixteen proteins were identified that were significantly up- or down-regulated in B lymphocytes of sensitized mice. Particularly differences in the expression of cyclophilin A, cofilin 1 and zinc finger containing CCHC domain protein 11 could be correlated to the function of B lymphocytes as initiators of T lymphocyte independent asthma-like responses.

Conclusion

This study revealed important alterations in the proteome of sensitized B cells in a mouse model of chemical-induced asthma, which will have an important impact on the B cell function.     

Functional Role of miRNAs: Key Players in Soybean Improvement

Soybean (Glycine max (L.) Merr) is an agro-economic crop growing across the world to cater nutrition for both human and animal feed due to the high oil and protein content in its edible seeds. The genes and QTLs associated with important agronomic traits in this crop have already been identified and validated for soybean cyst nematode (SCN), Phytophthora root and stem rot, Pythium root rot and aphid resistance, seed quality, nutrient values, and also employed for genetic improvement in soybean. In the last decade, micro RNAs (miRNAs) have been considered the effector molecules, so the detection and characterization of novel miRNAs in soybean have been taken up by several workers. The advancement in the strategy of sequencing and tools of bioinformatics during last decade has contributed to the discovery of many soybean miRNAs, thus miRNA can be used as a tool in molecular breeding studies, and this has opened new vistas for miRNA mediated genetic improvement of soybean to augment crop productivity as well as nutritional quality. This review addresses the current state of understanding of miRNAmediated stress responses, nutrient acquisition, plant development and crop production processes in soybean.     

DAZ Family Proteins,Key Players for Germ Cell Development

DAZ family proteins are found almost exclusively in germ cells in distant animal species. Deletion or mutations of their encoding genes usually severely impair either oogenesis or spermatogenesis or both. The family includes Boule (or Boll), Dazl (or Dazla) and DAZ genes. Boule and Dazl are situated on autosomes while DAZ, exclusive of higher primates, is located on the Y chromosome. Deletion of DAZ gene is the most common causes of infertility in humans. These genes, encoding for RNA binding proteins, contain a highly conserved RNA recognition motif and at least one DAZ repeat encoding for a 24 amino acids sequence able to bind other mRNA binding proteins. Basically, Daz family proteins function as adaptors for target mRNA transport and activators of their translation. In some invertebrate species, BOULE protein play a pivotal role in germline specification and a conserved regulatory role in meiosis. Depending on the species, DAZL is expressed in primordial germ cells (PGCs) and/or pre-meiotic and meiotic germ cells of both sexes. Daz is found in fetal gonocytes, spermatogonia and spermatocytes of adult testes. Here we discuss DAZ family genes in a phylogenic perspective, focusing on the common and distinct features of these genes, and their pivotal roles during gametogenesis evolved during evolution.     

Membrane Proteins: The Key Players of a Cancer Cell

Membrane proteins are involved in the prognosis of the most common forms of cancer. Membrane proteins are the hallmark of a cancer cell. The overexpressed membrane receptors are becoming increasingly important in cancer cell therapy. Current renewing therapy approaches based on receptor overexpression include; antibody therapy, nanocarrier drug delivery, and fluorescent tumor imaging in surgery. Gene profiling reveals cancer specific signatures and may identify membrane proteins that are related to cancer progression and lead to the development of improved therapy strategies in the future.     

Spinal Microglia and Astrocytes: Two Key Players in Chronic Visceral Pain Pathogenesis

Neurochemical Research - Chronic visceral pain (CVP) is one of the common symptoms of many diseases triggered by underlying diseases of the internal organs of the human body. Its causes include...     

ABA,ROS and NO are Key Players During Switchgrass Seed Germination

Seed dormancy and germination are complex physiological processes usually under hormonal control. Germination of seeds from many plants including switchgrass, are inhibited by ABA and promoted by NO or ROS. However, ABA apparently requires both ROS and NO as intermediates in its action, with ROS produced by membrane-bound NADPH-oxidases responsive to ABA. In switchgrass seeds, externally supplied hydrogen peroxide (ROS), but not NO will overcome ABA-imposed inhibition of germination. Stimulation of germination by external ROS can be partially blocked by NO-scavengers, suggesting that NO is required for seed germination in switchgrass as well as for ABA-induced inhibition of germination. Collectively, these data suggest that multiple mechanisms might be required to sense and respond to varying levels of ABA, NO and ROS in switchgrass seeds.Key Words: switchgrass, seed germination, ROS, hydrogen peroxide, ABA, nitric oxide     

Asthma as a disruption in iron homeostasis

Over several decades, asthma has evolved from being recognized as a single disease to include a diverse group of phenotypes with dissimilar natural histories, pathophysiologies, responses to treatment, and distinctive molecular pathways. With the application of Occam’s razor to asthma, it is proposed that there is one cause underlying the numerous phenotypes of this disease and that the responsible molecular pathway is a deficiency of iron in the lung tissues. This deficiency can be either absolute (e.g. asthma in the neonate and during both pregnancy and menstruation) or functional (e.g. asthma associated with infections, smoking, and obesity). Comparable associations between asthma co-morbidity (e.g. eczema, urticaria, restless leg syndrome, and pulmonary hypertension) with iron deficiency support such a shared mechanistic pathway. Therapies directed at asthma demonstrate a capacity to impact iron homeostasis, further strengthening the relationship. Finally, pathophysiologic events producing asthma, including inflammation, increases in Th2 cells, and muscle contraction, can correlate with iron availability. Recognition of a potential association between asthma and an absolute and/or functional iron deficiency suggests specific therapeutic interventions including inhaled iron.     

Pulmonary Thromboembolism Presenting as Asthma

When a patient presents with wheezing, pulmonary embolism is not usually considered as a possible cause. However, undoubtedly bronchoconstriction can be caused by pulmonary emboli and occasionally wheezing may be so obvious as to suggest a diagnosis of bronchial asthma. Eleven cases are reported in which wheezing was attributable to recurrent pulmonary emboli and one in which it was a clamant feature after a single embolic incident.     

Cd19-dependent activation of Akt kinase in B-lymphocytes

CD19 is rapidly phosphorylated upon B-cell antigen receptor (BCR) cross-linking, leading to the recruitment of downstream signaling intermediates. A prominent feature of CD19 signaling is the binding and activation of phosphoinositide 3-kinase (P13K), which accounts for the majority of PI3K activity induced by BCR ligation. Recent findings have implicated activation of the serine/threonine kinase Akt as imparting survival signals in a PI3K-dependent fashion. Using CD19-deficient B-lymphoma cells and mouse splenic B-cells, we show that CD19 is necessary for efficient activation of Akt following cross-linking of surface immunoglobulin or Igbeta. In the absence of CD19, Akt kinase activity is reduced and transient. In addition, coligation of CD19 with surface immunoglobulin leads to augmented Akt activity in a dose-dependent manner. Thus, CD19 is a key regulator of Akt activity in B-cells; as such it may contribute to pre-BCR or BCR-mediated cell survival in vivo.     

Stem cells and T- and B-lymphocytes in acute hypoxia

During the stepped rapid training of mice for hypoxia the number of colony-forming units in the blood and bone marrow increases and that in the spleen falls down. In acute hypoxic hypoxia there is an enhancement of the migration of stem hemopoietic cells and B-lymphocytes from the bone marrow and T-lymphocytes from the thymus.     

M-cholinergic receptors of B-lymphocytes during immune response in mice

The number of M-cholinergic receptors on spleen B-lymphocytes of CBA mice was determined using radioactive blocker 3H-Quinuclidinil benzilate. 3 and 4 days after the animals' immunization with ovalbumin the number of M-cholinergic receptors somewhat increased. Specific antigen attenuated M-cholinergic receptor expression on B-lymphocytes, most pronounced on day 4 after immunization, without affecting the receptor expression in control animals. Possible steric interaction between antigen-binding immunoglobulins and B-lymphocyte M-cholinergic receptors during immune response is suggested.