Multiple anti-inflammatory pathways triggered by resveratrol lead to amelioration of staphylococcal enterotoxin B-induced lung injury

ABSTRACTStaphylococcal enterotoxin B (SEB) causes food poisoning in humans. It is considered a biological weapon, and inhalation can trigger lung injury and sometimes respiratory failure. Being a superantigen, SEB initiates an exaggerated inflammatory response. While the role of microRNAs (miRNAs) in immune cell activation is getting increasing recognition, their role in the regulation of inflammatory disease induced by SEB has not been studied. In this investigation, we demonstrate that exposure to SEB by inhalation results in acute inflammatory lung injury accompanied by an altered miRNA expression profile in lung-infiltrating cells. Among the miRNAs that were significantly elevated, miR-155 was the most overexpressed. Interestingly, miR-155−/−mice were protected from SEB-mediated inflammation and lung injury. Further studies revealed a functional link between SEB-induced miR-155 and proinflammatory cytokine gamma interferon (IFN-γ). Through the use of bioinformatics tools, suppressor of cytokine signaling 1 (SOCS1), a negative regulator of IFN-γ, was identified as a potential target of miR-155. While miR-155−/−mice displayed increased expression ofSocs1, the overexpression of miR-155 led to its suppression, thereby enhancing IFN-γ levels. Additionally, the inhibition of miR-155 resulted in restoredSocs1expression. Together, our data demonstrate an important role for miR-155 in promoting SEB-mediated inflammation in the lungs throughSocs1suppression and suggest that miR-155 may be an important target in preventing SEB-mediated inflammation and tissue injury.

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Acute Lung Injury Induced by Staphylococcal enterotoxin B: Disruption of Terminal Vessels as a Mechanism of Induction of Vascular Leak

Microscopy and Microanalysis ◽

10.1017/s1431927612000190 ◽

2012 ◽

Vol 18 (3) ◽

pp. 445-452 ◽

Cited By ~ 16

Author(s):

Ali Imran Saeed ◽

Sadiye Amcaoglu Rieder ◽

Robert L. Price ◽

James Barker ◽

Prakash Nagarkatti ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Staphylococcal Enterotoxin ◽

Pulmonary Vasculature ◽

Tunel Staining ◽

Staphylococcal Enterotoxin B ◽

Vascular Leak ◽

Capillary Membrane ◽

Enterotoxin B ◽

Alveolar Capillary

AbstractThe current hypothesis of alveolar capillary membrane dysfunction fails to completely explain the severe and persistent leak of protein-rich fluid into the pulmonary interstitium, seen in the exudative phase of acute lung injury (ALI). The presence of intact red blood cells in the pulmonary interstitium may suggest mechanical failure of pulmonary arterioles and venules. These studies involved the pathological and ultrastructural evaluation of the pulmonary vasculature in Staphylococcal enterotoxin B (SEB)-induced ALI. Administration of SEB resulted in a significant increase in the protein concentration of bronchoalveolar lavage fluid and vascular leak in SEB-exposed mice compared to vehicle-treated mice. In vivo imaging of mice demonstrated the pulmonary edema and leakage in the lungs of SEB-administered mice. The histopathological studies showed intense clustering of inflammatory cells around the alveolar capillaries with subtle changes in architecture. Electron microscopy studies further confirmed the diffuse damage and disruption in the muscularis layer of the terminal vessels. Cell death in the endothelial cells of the terminal vessels was confirmed with TUNEL staining. In this study, we demonstrated that in addition to failure of the alveolar capillary membrane, disruption of the pulmonary arterioles and venules may explain the persistent and severe interstitial and alveolar edema.

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Detection of inflammation and oxidative lung injury in exhaled breath condensate of rats with acute lung injury due to Staphylococcal enterotoxin B

Journal of Breath Research ◽

10.1088/1752-7155/7/2/026003 ◽

2013 ◽

Vol 7 (2) ◽

pp. 026003 ◽

Cited By ~ 2

Author(s):

Rekha Solomon ◽

Hitesh Sandhu ◽

Suwannee Phumeetham ◽

Keshava Murthy Narayana Gowda ◽

Sabrina M Heidemann

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Exhaled Breath Condensate ◽

Staphylococcal Enterotoxin ◽

Staphylococcal Enterotoxin B ◽

Exhaled Breath ◽

Enterotoxin B ◽

Breath Condensate

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Δ9Tetrahydrocannabinol attenuates Staphylococcal enterotoxin B-induced inflammatory lung injury and prevents mortality in mice by modulation of miR-17-92 cluster and induction of T-regulatory cells

British Journal of Pharmacology ◽

10.1111/bph.13026 ◽

2015 ◽

Vol 172 (7) ◽

pp. 1792-1806 ◽

Cited By ~ 22

Author(s):

R Rao ◽

P S Nagarkatti ◽

M Nagarkatti

Keyword(s):

Lung Injury ◽

T Regulatory Cells ◽

Staphylococcal Enterotoxin ◽

Staphylococcal Enterotoxin B ◽

Regulatory Cells ◽

Enterotoxin B

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CD44 as a novel target for treatment of staphylococcal enterotoxin B-induced acute inflammatory lung injury

Clinical Immunology ◽

10.1016/j.clim.2012.05.001 ◽

2012 ◽

Vol 144 (1) ◽

pp. 41-52 ◽

Cited By ~ 14

Author(s):

Jingping Sun ◽

Gabriela P. Law ◽

Christy C. Bridges ◽

Robert J. McKallip

Keyword(s):

Lung Injury ◽

Staphylococcal Enterotoxin ◽

Staphylococcal Enterotoxin B ◽

Enterotoxin B ◽

Novel Target

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Staphylococcal Enterotoxin B-Induced Acute Inflammation Is Inhibited by Dexamethasone: Important Role of CXC Chemokines KC and Macrophage Inflammatory Protein 2

Infection and Immunity ◽

10.1128/iai.71.5.2542-2547.2003 ◽

2003 ◽

Vol 71 (5) ◽

pp. 2542-2547 ◽

Cited By ~ 27

Author(s):

Rene Schramm ◽

Henrik Thorlacius

Keyword(s):

Acute Inflammation ◽

Staphylococcal Enterotoxin ◽

Neutrophil Recruitment ◽

Time Dependent ◽

Maximal Response ◽

Staphylococcal Enterotoxin B ◽

Inflammatory Protein ◽

Enterotoxin B ◽

Anti Inflammatory ◽

Macrophage Inflammatory Protein

ABSTRACT This study was conducted to examine the anti-inflammatory mechanisms of dexamethasone during leukocyte recruitment and expression of the CXC chemokines macrophage inflammatory protein 2 (MIP-2) (CXCL2) and cytokine-induced neutrophil chemoattractant (KC) (CXCL1) in staphylococcal enterotoxin B (SEB)-induced acute inflammation. To do this, SEB was injected into murine air pouches with or without dexamethasone pretreatment for 2 h. SEB induced infiltration of leukocytes in a dose- and time-dependent manner, with the maximal response observed after 4 h of treatment with 10 μg of SEB. The recruited leukocytes comprised more than 77% neutrophils. Moreover, SEB challenge (10 μg) provoked time-dependent secretion of CXC chemokines, which peaked after 1 h. Local administration of antibodies against MIP-2 and KC significantly reduced SEB-triggered neutrophil accumulation by 38 and 59%, respectively. Dexamethasone (10 mg kg−1) significantly decreased neutrophil recruitment by 82% and reduced secretion of MIP-2 and KC by 89 and 85%, respectively, in response to SEB challenge. Our data demonstrate that dexamethasone potently inhibits neutrophil recruitment in SEB-induced inflammation. Moreover, we provide evidence that MIP-2 and KC are key mediators in the neutrophil response to SEB. Furthermore, our findings demonstrate that dexamethasone attenuates SEB-induced expression of MIP-2 and KC. Thus, this study elucidates important signaling pathways of SEB-induced neutrophil recruitment and anti-inflammatory mechanisms of action of dexamethasone.

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