American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2011
Obstructive sleep apnea: brain structural changes and neurocognitive function before and after treatment.
Obstructive sleep apnea (OSA) is commonly associated with neurocognitive impairments that have not been consistently related to specific brain structure abnormalities. Knowledge of the brain structures involved in OSA and the corresponding functional implications could provide clues to the pathogenesis of cognitive impairment and its reversibility in this disorder. ⋯ The cognitive and structural deficits in OSA may be secondary to sleep deprivation and repetitive nocturnal intermittent hypoxemia. These negative effects may be recovered by consistent and thorough treatment. Our findings highlight the importance of early diagnosis and successful treatment of this disorder.
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Am. J. Respir. Crit. Care Med. · May 2011
Interferon-γ production by neutrophils during bacterial pneumonia in mice.
Neutrophils are usually the first circulating leukocytes to respond during bacterial pneumonia. Their expression of oxidants, proteases, and other mediators present in granules is well documented, but their ability to produce mediators through transcription and translation after migration to an inflammatory site has been appreciated only more recently. Interferon (IFN)-γ is a cytokine with many functions important in host defense and immunity. ⋯ S. pneumoniae and S. aureus, but not P. aeruginosa and E. coli, induce emigrated neutrophils to produce IFN-γ within 24 hours. Hck/Fgr/Lyn, Rac2, and NADPH oxidase are required for IFN-γ production. IFN-γ facilitates bacterial clearance at least in part through regulating formation of neutrophil extracellular traps. Differential expression by neutrophils of microRNAs that target the 3' untranslated region of the IFN-γ gene may contribute to the pathogen-specific regulation of translation.
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Am. J. Respir. Crit. Care Med. · May 2011
RIG-like helicase innate immunity inhibits vascular endothelial growth factor tissue responses via a type I IFN-dependent mechanism.
Vascular endothelial growth factor (VEGF) regulates vascular, inflammatory, remodeling, and cell death responses. It plays a critical role in normal pulmonary physiology, and VEGF excess and deficiency have been implicated in the pathogenesis of asthma and chronic obstructive pulmonary disease, respectively. Although viruses are an important cause of chronic obstructive pulmonary disease exacerbations and innate responses play an important role in these exacerbations, the effects of antiviral responses on VEGF homeostasis have not been evaluated. ⋯ These studies demonstrate that poly(I:C) and respiratory viruses inhibit VEGF-induced tissue responses and adaptive helper T-cell type 2 inflammation and highlight the importance of a RLH- and type I IFN receptor-dependent pathway(s) in these regulatory events. They define a novel link between VEGF and antiviral and RLH innate immune responses and a novel pathway that regulates pulmonary VEGF activity.