TNF-alpha- and IFN-gamma-mediated signal transduction pathways: effects on glial cell gene expression and function.

Elucidation of the structure and function of the hydrophobic surfactant protein (SP-B) and the SP-B gene has provided critical insight into surfactant homeostasis and control of respiratory epithelial cell gene expression. Surfactant protein B, in concert with surfactant protein A (SP-A), surfactant protein C (SP-C), and surfactant phospholipids, contributes to the structure and function of surfactant particles, determining surface activities and pathways by which surfactant phospholipids and proteins are processed, routed, packaged, and secreted from lamellar bodies by type II epithelial cells. After secretion, SP-B plays an essential role in determining the structure of tubular myelin, the stability and rapidity of spreading, and the recycling of surfactant phospholipids. The biochemical and structural signals underlying the homeostasis of alveolar surfactant are likely mediated by interactions between the surfactant proteins and phospholipids producing discrete structural forms that vary in size, aproprotein, and phospholipid content. Distinctions in structure, protein, and size are likely to determine the function of surfactant particles, their catabolism, or recycling by alveolar macrophages and airway epithelial cells. Analysis of the genetic controls governing the SP-B gene has led to the definition of DNA-protein interactions that determine respiratory epithelial cell gene expression in general. The important role of SP-B in lung function was defined by the study of a lethal neonatal respiratory disease, hereditary SP-B deficiency, caused by mutations in the human SP-B gene.

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Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

10.2172/1037347 ◽

2012 ◽

Author(s):

Daila S. Gridley, PhD

Keyword(s):

Gene Expression ◽

Low Dose ◽

Acute Radiation ◽

Th Cell ◽

Cell Gene Expression ◽

And Function ◽

Cell Gene

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Epithelial Cell Gene Expression Induced by IntracellularStaphylococcus aureus

International Journal of Microbiology ◽

10.1155/2009/753278 ◽

2009 ◽

Vol 2009 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Xianglu Li ◽

William G. Fusco ◽

Keun S. Seo ◽

Kenneth W. Bayles ◽

Erin E. Mosley ◽

...

Keyword(s):

Gene Expression ◽

Signal Transduction ◽

Stress Responses ◽

Dna Microarrays ◽

Cholesterol Biosynthesis ◽

Transcriptional Level ◽

Cell Monolayers ◽

Cell Gene Expression ◽

Cellular Stress Responses ◽

Cell Gene

HEp-2 cell monolayers were cocultured with intracellularStaphylococcus aureus, and changes in gene expression were profiled using DNA microarrays. IntracellularS. aureusaffected genes involved in cellular stress responses, signal transduction, inflammation, apoptosis, fibrosis, and cholesterol biosynthesis. Transcription of stress response and signal transduction-related genes includingatf3, sgk, map2k1, map2k3, arhb, andarhewas increased. In addition, elevated transcription of proinflammatory genes was observed fortnfa, il1b, il6, il8, cxcl1, ccl20, cox2,andpai1. Genes involved in proapoptosis and fibrosis were also affected at transcriptional level by intracellularS. aureus. Notably, intracellularS. aureusinduced strong transcriptional down-regulation of several cholesterol biosynthesis genes. These results suggest that epithelial cells respond to intracellularS. aureusby inducing genes affecting immunity and in repairing damage caused by the organism, and are consistent with the possibility that the organism exploits an intracellular environment to subvert host immunity and promote colonization.

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Evidence for the involvement of distinct signal transduction pathways in the regulation of constitutive and interferon gamma-dependent gene expression of NADPH oxidase components (gp91-phox, p47-phox, and p22- phox) and high-affinity receptor for IgG (Fc gamma R-I) in human polymorphonuclear leukocytes

Blood ◽

10.1182/blood.v79.3.735.735 ◽

1992 ◽

Vol 79 (3) ◽

pp. 735-744 ◽

Cited By ~ 32

Author(s):

MA Amezaga ◽

F Bazzoni ◽

C Sorio ◽

F Rossi ◽

MA Cassatella

Keyword(s):

Gene Expression ◽

Signal Transduction ◽

Steady State ◽

Polymorphonuclear Leukocytes ◽

Signal Transduction Pathways ◽

Ifn Gamma ◽

High Affinity ◽

Steady State Levels ◽

Human Polymorphonuclear Leukocytes ◽

I Gene

Abstract We recently showed that mRNA levels coding the high-affinity Fc gamma receptor for IgG (Fc gamma R-I, CD64) and two of the components of the phagocytic superoxide anion-generating system--the heavy-chain subunit of cytochrome b558 (gp91-phox) and the 47-Kd cytosolic factor (p47- phox)--are modulated by interferon gamma (IFN-gamma). In this study, we examined whether dexamethasone (DEX) affects gp91-phox and p47-phox mRNA expression of human polymorphonuclear leukocytes (PMN), treated or not with IFN-gamma. We also investigated whether staurosporine, a general inhibitor of protein kinases, influences gp91-phox, p47-phox, and Fc gamma R-I gene expression in PMN treated with or without IFN- gamma. We found that (1) gp91-phox mRNA steady-state levels, expressed in control or IFN-gamma-treated PMN, were significantly inhibited, in a dose-dependent fashion, by both DEX and staurosporine; (2) p47-phox mRNA steady-state levels, expressed in control or IFN-gamma-treated PMN, were not influenced by DEX, but were markedly depressed by staurosporine; (3) no changes of spectrophotometric cytochrome b558 were found in PMN treated for up to 20 hours with the inhibitors, regardless of the presence of IFN-gamma; (4) both DEX and staurosporine dose-dependently inhibited IFN-gamma-induced Fc gamma R-I mRNA and protein expression; and (5) stability of gp91-phox and Fc gamma R-I messages in IFN-gamma-treated PMN was not altered by the presence of DEX. Our results demonstrate that gp91-phox, p47-phox, and Fc gamma R-I gene expression of PMN is governed by specific and independent biochemical pathways. Moreover, IFN-gamma activates different signal transduction pathways to modulate mRNA expression of gp91-phox, p47- phox, and Fc gamma R-I.

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