Abstract
Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome characterized by diffuse alveolar damage usually secondary to an intense host inflammatory response of the lung to a pulmonary or extrapulmonary infectious or non-infectious insult often leading to the development of intra-alveolar and interstitial fibrosis. Curcumin, the principal curcumoid of the popular Indian spice turmeric, has been demonstrated as an anti-oxidant and anti-inflammatory agent in a broad spectrum of diseases. Using our well-established model of reovirus 1/L-induced acute viral pneumonia, which displays many of the characteristics of the human ALI/ARDS, we evaluated the anti-inflammatory and anti-fibrotic effects of curcumin. Female CBA/J mice were treated with curcumin (50 mg/kg) 5 days prior to intranasal inoculation with 10(7)pfu reovirus 1/L and daily, thereafter. Mice were evaluated for key features associated with ALI/ARDS. Administration of curcumin significantly modulated inflammation and fibrosis, as revealed by histological and biochemical analysis. The expression of IL-6, IL-10, IFNγ, and MCP-1, key chemokines/cytokines implicated in the development of ALI/ARDS, from both the inflammatory infiltrate and whole lung tissue were modulated by curcumin potentially through a reduction in the phosphorylated form of NFκB p65. While the expression of TGFß1 was not modulated by curcumin, TGFß Receptor II, which is required for TGFß signaling, was significantly reduced. In addition, curcumin also significantly inhibited the expression of α-smooth muscle actin and Tenascin-C, key markers of myofibroblast activation. This data strongly supports a role for curcumin in modulating the pathogenesis of viral-induced ALI/ARDS in a pre-clinical model potentially manifested through the alteration of inflammation and myofibroblast differentiation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Chemokine CCL2 / genetics
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Chemokine CCL2 / immunology
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Curcumin / pharmacology*
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Disease Models, Animal
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Female
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Fibrosis / prevention & control
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Gene Expression / drug effects
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Humans
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Inflammation / prevention & control
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Injections, Intraperitoneal
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Interferon-gamma / genetics
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Interferon-gamma / immunology
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Interleukin-10 / genetics
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Interleukin-10 / immunology
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Interleukin-6 / genetics
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Interleukin-6 / immunology
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Mice
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Mice, Inbred CBA
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Orthoreovirus, Mammalian / growth & development
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / immunology
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / antagonists & inhibitors
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Receptors, Transforming Growth Factor beta / genetics
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Receptors, Transforming Growth Factor beta / immunology
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Reoviridae Infections / complications
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Reoviridae Infections / drug therapy*
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Reoviridae Infections / immunology
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Reoviridae Infections / pathology
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Respiratory Distress Syndrome / drug therapy*
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Respiratory Distress Syndrome / etiology
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Respiratory Distress Syndrome / immunology
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Respiratory Distress Syndrome / pathology
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Signal Transduction / drug effects
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Tenascin / genetics
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Tenascin / immunology
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Transcription Factor RelA / genetics
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Transcription Factor RelA / immunology
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Transforming Growth Factor beta1 / genetics
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Transforming Growth Factor beta1 / immunology
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Ccl2 protein, mouse
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Chemokine CCL2
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IL10 protein, mouse
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Interleukin-6
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Receptors, Transforming Growth Factor beta
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Tenascin
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Transcription Factor RelA
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Transforming Growth Factor beta1
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Interleukin-10
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Interferon-gamma
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II
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Curcumin