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Enhanced prostaglandin production during fungal infection could be an important factor in promoting fungal colonization and chronic infection. Host cells are one source of prostaglandins; however, another potential source of prostaglandins is the fungal pathogen itself. Our objective was to determine if the pathogenic yeasts Cryptococcus neoformans and(More)
Leukotrienes are bronchoconstrictor and vasoactive lipid mediators that are targets in the treatment of asthma. Although they are increasingly recognized to exert broad proinflammatory effects, their role in innate immune responses is less well appreciated. These molecules are indeed synthesized by resident and recruited leukocytes during infection. Acting(More)
Idiopathic pulmonary fibrosis (IPF) is a progressive disorder characterized by inflammation, fibroblast proliferation, and accumulation of extracellular matrix proteins. Leukotrienes (LTs) are pro-inflammatory and pro-fibrogenic mediators derived from the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism. They are thought to play a role in a(More)
Chemokines play critical roles in HIV-1 infection, serving both to modulate viral replication and to recruit target cells to sites of infection. Interferon-gamma-inducible protein 10 (IP-10/CXCL10) is a C-X-C chemokine that acts specifically upon activated T cells and macrophages and attracts T cells into the cerebrospinal fluid (CSF) in HIV-associated(More)
Since macrophages are a source of increased PGE(2) in AIDS, we investigated the role of PGE(2) in the replication of HIV-1 in these cells. PGE(2) inhibited HIV-1 replication measured by reverse transcriptase in human monocyte-derived macrophage (MDM). Treatment of MDM with the PGE(1) analog misoprostol, the adenylate cyclase activator forskolin, and the(More)
Severe asthma often requires high-dose corticosteroid therapy. However, steroid therapy is fraught with many side effects. There are conflicting reports in the literature regarding the role of methotrexate in reducing the steroid requirements of these patients. This study examined the role of low-dose methotrexate in the management of steroid-dependent(More)
Previous animal studies support the presence of an upper airway reflex mechanism that when blocked by topical anesthesia of the upper airway results in upper airway occlusion. We sought a similar reflex mechanism in humans. Nine normal male volunteers 20 to 28 yr of age underwent 3 successive overnight sleep studies: a control study (C); a study in which(More)
The enzyme 5-lipoxygenase (5-LO) catalyzes the first two steps in the metabolism of arachidonic acid to leukotrienes, substances which play pivotal roles both in normal host defense and in pathologic states of inflammation. Recent studies in granulocytic cells have shown that activation of 5-LO involves its Ca(2+)-dependent translocation from cytosol to(More)
Leukotrienes (LTs) are potent mediators of inflammation derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. Although they are known to enhance leukocyte recruitment and function, their role in antimicrobial host defense has not been established. To determine the role of endogenous LTs in the host response to pulmonary infection,(More)
To characterize the role of GM-CSF in pulmonary fibrosis, we have studied bleomycin-induced fibrosis in wild-type mice vs mice with a targeted deletion of the GM-CSF gene (GM-CSF-/- mice). Without GM-CSF, pulmonary fibrosis was worse both histologically and quantitatively. These changes were not related to enhanced recruitment of inflammatory cells because(More)