Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome
Authors: Fangfang Zhang
Sreedevi Avasarala
Guangliang Liu
Steven D London
Lucille London
Ruixue Wang
Journal: PloS one (2013)
Discipline: Multidisciplinary
Keywords: Acute Respiratory Distress Syndrome (ARDS); Curcumin; Anti-inflammatory; Anti-fibrotic effects; Reovirus 1/L
Affiliations: Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, New York, United States of America.

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. 

Retracted: No

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 August 2015 correction: https: journals.plos.org plosone article?id=10.1371 journal.pone.0134982 *In Fig 4A, as the result of an error in preparation of the Western blot images, incorrect bands were shown for u00df-actin, saline-treated u03b1-SMA and saline-treated Tenascin. Bands labelled u00df-actin were taken from the u03b1-SMA blot by mistake; the band labelled saline-treated u03b1-SMA was taken from a different lane showing curcumin-treated lysate in the same blot; the band labelled saline-treated Tenascin was from a different blot. Additionally, u03b1-SMA, E-cadherin and u00df-actin expression were measured on a single blot that was stripped and re-probed multiple times, while Tenascin (TN-C) was probed on a different blot in an independent experiment with u00df-actin antibodies used concurrently. The u00df-actin bands from the independent Tenascin blot were not shown in the original Fig 4A. Here we provide a revised Fig 4 showing the correct u00df-actin and u03b1-SMA bands, and a revised Fig 4 legend. The original uncropped blot images are provided as a supplementary file, with arrows indicating the correct sized bands. Multiple exposures are provided for the E-cadherin blot. The revised figure has been prepared using lanes 1, 6, and 7 of the original E-cadherin blot to match the lanes used from the u00df-actin and u03b1-SMA blots; the original published figure used lanes 1, 4, and 5 (lanes 4 and 6 both used lysates from untreated mice on day 14; lanes 5 and 7 both used lysates from curcumin-treated mice on day 14). The errors in the original figure do not affect the results demonstrated in Fig 4A, which are further confirmed by the additional methods shown in Fig 4B and 4C.* ,