American Journal of Respiratory Cell and Molecular Biology 

About: American Journal of Respiratory Cell and Molecular Biology is an academic journal published by American Thoracic Society. The journal publishes majorly in the area(s): Lung & Lung injury. It has an ISSN identifier of 1044-1549. Over the lifetime, 6607 publications have been published receiving 354629 citations. The journal is also known as: Red journal & AJRCMB online.

An Official American Thoracic Society Workshop Report: Features and Measurements of Experimental Acute Lung Injury in Animals

Abstract: Acute lung injury (ALI) is well defined in humans, but there is no agreement as to the main features of acute lung injury in animal models. A Committee was organized to determine the main features that characterize ALI in animal models and to identify the most relevant methods to assess these features. We used a Delphi approach in which a series of questionnaires were distributed to a panel of experts in experimental lung injury. The Committee concluded that the main features of experimental ALI include histological evidence of tissue injury, alteration of the alveolar capillary barrier, presence of an inflammatory response, and evidence of physiological dysfunction; they recommended that, to determine if ALI has occurred, at least three of these four main features of ALI should be present. The Committee also identified key "very relevant" and "somewhat relevant" measurements for each of the main features of ALI and recommended the use of least one "very relevant" measurement and preferably one or two additional separate measurements to determine if a main feature of ALI is present. Finally, the Committee emphasized that not all of the measurements listed can or should be performed in every study, and that measurements not included in the list are by no means "irrelevant." Our list of features and measurements of ALI is intended as a guide for investigators, and ultimately investigators should choose the particular measurements that best suit the experimental questions being addressed as well as take into consideration any unique aspects of the experimental design.

Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury.

Abstract: Accumulating evidence suggests that oxidative stress plays a central role in the pathogenesis of many pulmonary diseases including adult respiratory distress syndrome, emphysema, asthma, bronchopulmonary dysplasia, and interstitial pulmonary fibrosis. The morbidity and mortality of these diseases remain high even with optimal medical management. In our attempts to devise new therapies for these disorders, it is crucial to improve our understanding of the basic mechanism(s) of oxidant-induced lung injury. A major line of investigation seeks to characterize the cellular and molecular responses of the lung to oxidant insults. Much progress has been made in our understanding of the role of the "classic" antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) in mediating the lung's resistance against oxidant lung injury. However, it is becoming clear that other oxidant-induced gene products may also play vital roles in the lung's adaptive and/or protective response to oxidative stress. One such stress-response protein is heme oxygenase-1, HO-1. Since the identification of HO-1 in 1968, many of the studies involving this enzyme were understandably focused on the regulation and function of HO-1 in heme metabolism. This emphasis is self-evident as HO-1 catalyzes the first and rate-limiting step in heme degradation. Interestingly, however, evidence accumulated over the past 25 years demonstrates that HO-1 is induced not only by the substrate heme but also by a variety of non-heme inducers such as heavy metals, endotoxin, heat shock, inflammatory cytokines, and prostaglandins. The chemical diversity of HO-1 inducers led to the speculation that HO-1, besides its role in heme degradation, may also play a vital function in maintaining cellular homeostasis. Further support for this hypothesis was provided by Tyrrell and colleagues who showed in 1989 that HO-1 is also highly induced by a variety of agents causing oxidative stress. Subsequently, many investigators have focused their attention on the function and regulation of HO-1 in various in vitro and in vivo models of oxidant-mediated cellular and tissue injury. The magnitude of HO-1 induction after oxidative stress and the wide distribution of this enzyme in systemic tissues coupled with the intriguing biological activities of the catalytic byproducts, carbon monoxide, iron, and bilirubin, makes HO-1 a highly attractive and interesting candidate stress-response protein which may play key role(s) in mediating protection against oxidant-mediated lung injury. This review will focus on the current understanding of the physiological significance of HO-1 induction and the molecular regulation of HO-1 gene expression in response to oxidative stress. We hope that this discussion will stimulate interest and investigations into a field which is still largely uncharted in the pulmonary research community.

The role of nuclear factor-kappa B in cytokine gene regulation.

Abstract: Transcription factors are DNA-binding proteins that regulate gene expression. Nuclear factor-κB (NF-κB) is a critical transcription factor for maximal expression of many cytokines that are involved in the pathogenesis of inflammatory diseases, such as adult respiratory distress syndrome (ARDS) and sepsis syndrome. Activation and regulation of NF-κB are tightly controlled by a group of inhibitory proteins (IκB) that sequester NF-κB in the cytoplasm of immune/inflammatory effector cells. NF-κB activation involves signaled phosphorylation, ubiquitination, and proteolysis of IκB. Liberated NF-κB migrates to the nucleus, where it binds to specific promoter sites and activates gene transcription. The activation of NF-κB initiates both extracellular and intracellular regulatory events that result in autoregulation of the inflammatory cascade through modulation of NF-κB activation. Recently, activation of NF-κB has been linked to ARDS and has been shown to be a critical proximal step in the initiation of neutroph...

CFTR expression and chloride secretion in polarized immortal human bronchial epithelial cells.

Abstract: A major limitation in the study of vectorial ion transport, secretion, and differentiated function in the human airway epithelium has been the lack of suitable cell culture systems. Progress in this direction has been made through the transformation of primary cultured epithelial cells. However, these transformants tend to lose differentiated properties with increasing serial passage, particularly following crisis. The suc­ cessful establishment of a postcrisis SV40 large T-antigen transformed epithelial cell line derived from human bronchial epithelium is described. This cell line, 16HBEI40-, retains differentiated epithelial mor­ phology and functions. Cell cultures show the presence of tight junctions and cilia, and monolayers gener­ ate transepithelial resistance, as measured in Ussing chambers, and retain iJ-adrenergic stimulation of cAMP-dependent chloride ion transport, measured either by ,6CI- efflux or as short-circuit current in Ussing chambers. The cells also increase chloride transport in response to bradykinin or calcium iono­ phore. In addition, 16HBE140-cells express levels of both the cystic fibrosis transmembrane conductance regulator (CFTR) mRNA and protein readily detectable by Northern and Western hybridization analysis, respectively. These cells provide a valuable resource for studying the modulation of CFTR and its role in regulation of chloride ion transport in human airway epithelium as well as other aspects of human airway cell biology. The human airway epithelium is pseudostratified, consisting of highly organized layers of polar cells with specific dif­ ferentiated functions. It includes ciliated columnar cells, basal cells, and secretory goblet cells that are linked by tight junctions. The tight junctions provide a barrier between the airway lumen and the underlying tissues and divide the epi­ thelial cells into apical and basolateral domains. Both of these plasma membrane compartments contain different populations of proteins that allow for directional flux of ions

A Polymorphism* in the 5 ′ Flanking Region of the CD14 Gene Is Associated with Circulating Soluble CD14 Levels and with Total Serum Immunoglobulin E

Abstract: Total serum immunoglobulin (Ig)E levels are genetically regulated, but the mechanism of inheritance is not well understood. Cytokines produced by T-helper (Th)1 and Th2 lymphocytes control IgE synthesis. Bacterial antigens may favor the development of Th1 cells from naive CD4-positive T cells through a CD14-dependent pathway. CD14 is constitutively expressed on the surface of monocytes and macrophages, and is also present in serum in a soluble form (sCD14). The CD14 gene maps to chromosome 5q31.1, a candidate region for loci regulating total serum IgE. We hypothesized that genetic variants in the CD14 gene could influence Th-cell differentiation and thus total serum IgE. We identified a C-to-T transition at base pair −159 from the major transcription start site (CD14/−159). Among 481 children recruited from a general population sample, frequency of allele C was 51.4%. TT homozygotes had significantly higher sCD14 levels than did carriers of both the CC and CT genotypes (P = 0.01). TT homozygotes also had ...