Abstract:
Background: Acute lung injury (ALI) it is a very serious illness characterized by inflammatory lung swelling, leading to acute hypoxic respiratory failure. It is frequently linked to multiorgan failure caused by an exaggerated immune response, in which the excessive release of proinflammatory cytokines from stimulated inflammatory cells is a key factor in its progression
Objective: c-Raf G-protein has been shown to regulate inflammation we predicted that c-Raf could regulate neutrophil infiltration in LPS induced sepsis in mice model.
Methods: Group of 18 Albino mice (6 weeks age, weighing 26±2 grams) were randomly assigned to 3 groups: the control group (received normal saline intraperitoneally, n=6), the LPS group (50 mg/kg LPS was administered intraperitoneally, n=6), the GW5074 + LPS group (2 mg/kg of the selective c-Raf inhibitor GW5074 was given intraperitoneally 15 minutes before LPS injection, n=6). After 24 hours, the mice were sacrificed, and inflammatory cell counts, proinflammatory cytokines (TNF-α, IL-1β, MPO activity, CXCL-2, IL-6), were measured. The lungs were then isolated for molecular target analysis, histopathological, and immunohistochemical evaluations.
Results: Resemble to the LPS group, pretreatment of mice with c-Raf inhibitor significantly decreased MPO, CXCL-2, TNF-α, IL-1β and IL-6, activity. GW5074 weakened migration and infiltration of inflammatory cells, showing a marked reduce in MPO (6.0 ±0.2 vs. 2.2 ±2.0 P<0.05) as well as CXCL-2 (132.8 ± 2.0 vs. 80.4± 6.0 P<0.05) in the sham, LPS, and GW5074 + LPS. Additionally, IL-6 levels in treatment group significantly decrease compared with LPS group (123 ± 4.0 vs. 71.2 ± 6.0 P<0.05).
Conclusions: The conclusions of this study suggest that c-Raf may have anti-inflammatory and protective effects against LPS-stimulated ALI in mice. c-Raf restrain proinflammatory cytokines that play a critical role in the early stages of the inflammatory response, indicating that blocking the c-Raf signaling pathway could be a potential mechanism for mitigating sepsis. Therefore, c-Raf may serve as a novel therapeutic approach for treating pulmonary inflammation.
Biography:
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