Simvastatin attenuates inflammatory process on LPS-induced acute lung injury in mice

Haute, Gabriela Viegas; Luft, Carolina; Pedrazza, Leonardo; Antunes, Géssica Luana; Silveira, Josiane Silva; Basso, Bruno de Souza; Levorse, Vitor Giancarlo Schneider; Bastos, Matheus Scherer; Melo, Denizar Alberto da Silva; Rodrigues, Kétlin Fernanda; Garcia, Maria Cláudia Rosa; Costa, Mariana Severo da; Matzenbacher, Lucas Strasburger; Kaiber, Daniela Benvenutti; Donadio, Márcio Vinı́cius Fagundes; Gracia‐Sancho, Jordi; Oliveira, Jarbas Rodrigues de

doi:10.1016/j.resp.2022.104002

Cited by 4 publications

(1 citation statement)

References 45 publications

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“…ARDS is characterized by influx of inflammatory cells such as neutrophils and recruited macrophages, acute diffuse alveolar damage, and protein rich exudates in alveolar spaces (3). Lung macrophages play a key role in ARDS pathogenesis (4,5) as they are major players in both initiation and resolution of lung inflammation (6). Furthermore, anti-inflammatory pathways play an important role to control the severity of ARDS.…”

Section: Introductionmentioning

confidence: 99%

Specificity of CD200/CD200R pathway in LPS-induced lung inflammation

et al. 2022

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IntroductionAt lung mucosal surfaces, immune cells must initiate inflammatory response against pathogen without inducing tissue damage. Loss of this equilibrium can lead to acute respiratory distress syndrome (ARDS), a severe lung inflammatory disease characterized by excessive inflammation and dysregulation of anti-inflammatory pathways.MethodsTo investigate the role of anti-inflammatory pathway CD200/CD200R in lung inflammatory response, we administered LPS intratracheally in CD200 KO and wild type (WT) rats. Inflammation was evaluated using bronchoalveolar lavage (BAL) cellularity. Lung injury was measured by total protein level in BAL fluid, and levels of proinflammatory cytokines (TNF, IL-6) and chemokines (CXCL2, CCL2) were determined in BAL supernatants. In a second series of experiments, recombinant CD200Fc was administered to KO rats to restore the anti-inflammatory response.ResultsAt baseline, CD200 KO rats did not show sign of inflammation, however KO rats had lower number of alveolar macrophages. In addition, LPS administration induced greater pulmonary edema in CD200 KO rats. This was accompanied with a higher recruitment of neutrophils as well as levels of TNF, IL-6, CXCL2, and CCL2 in BAL compared to WT rats. CD200Fc administration in KO rats reduced neutrophil accumulation and TNF and CXCL2 levels in BAL. Interestingly, the increased inflammatory response of CD200 KO rats could be attributed to greater activation potential of alveolar macrophages with higher levels of ERK and P-ERK MAPK.ConclusionThis study shows that lung inflammatory response is exacerbated in absence of CD200 in an experimental model of ARDS in rats. In addition, CD200/CD200R pathway shows selective regulation of acute lung inflammation and cannot completely abrogate the complex LPS-induced inflammatory response. However, addition of CD200 agonist in a multi-target therapy strategy could have beneficial impacts.

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Section: Introductionmentioning

confidence: 99%

Specificity of CD200/CD200R pathway in LPS-induced lung inflammation

et al. 2022

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A three-phase strategy of bionic drug reservoir scaffold by 3D printing and layer-by-layer modification for chronic relapse management in traumatic osteomyelitis

Zhang,

Xu,

et al. 2024

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A Simvastatin-Loaded Nanoliposome Delivery System for Sepsis-Induced Acute Lung Injury

Yang,

Yue

2024

j biomed nanotechnol

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To enhance the treatment of acute lung injury (ALI) induced by sepsis and optimize the clinical efficacy of simvastatin (SV), we develop SV-loaded nanoliposomes (SV/NLC) as a novel drug delivery system. The NLCs exhibited a particle size of approximately 165 nm, which increased to around 195 nm upon SV loading. NLCs significantly prolonged the half-life of SV by nearly five-fold and improved its penetration into EA.hy926 cells, demonstrating excellent biocompatibility and targeted delivery for ALI therapy. In the rat model of ALI, the SV/NLC effectively reduced the lung wet/dry ratio and the levels of inflammatory factor and albumin in the alveoli, thus improving the alveolar gas exchange function and blood oxygenation. The SV/NLC group demonstrated superior suppression of oxidative stress within lung tissues compared to other groups. Notably, treatment with SV reduction in TLR4, MyD88, and NF-κB P65 levels in lung tissues from ALI rat models. This effect was particularly pronounced in the SV/NLC group. Furthermore, SV can effectively mitigate inflammatory responses and oxidative stress in ALI treatment by modulating the TLR4/NF-κB signaling pathway. In conclusion, our findings suggest that SV can exert therapeutic effects against sepsis-induced ALI through inhibition of the TLR4/NF-κ and mitigate inflammatory response and oxidative stress.

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Simvastatin attenuates inflammatory process on LPS-induced acute lung injury in mice

Cited by 4 publications

References 45 publications

Specificity of CD200/CD200R pathway in LPS-induced lung inflammation

Specificity of CD200/CD200R pathway in LPS-induced lung inflammation

A three-phase strategy of bionic drug reservoir scaffold by 3D printing and layer-by-layer modification for chronic relapse management in traumatic osteomyelitis

A Simvastatin-Loaded Nanoliposome Delivery System for Sepsis-Induced Acute Lung Injury

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