Therapeutic potential of c-Raf in LPS-stimulated acute lung injury: Anti-inflammatory and protective effects in mice model

Background and objective: Acute lung injury (ALI) it considered as a very serious illness characterized by inflammatory lung swelling, leading to acute hypoxic respiratory failure. 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: 18 albino mice (6 weeks age, weighing 26±2 grams) were randomly assigned to three groups: the control group (they were injected by normal saline intraperitoneally, n=6), the LPS (lipopolysaccharide) group (50 mg/kg LPS Were injected intraperitoneally, n=6), the GW5074 + LPS group (2 mg/kg of the selective c-Raf inhibitor GW5074 were given intraperitoneally 15 minutes before LPS injection, n=6). After 24 hours, the mice were sacrificed, then 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). Conclusion: The conclusions of this research propose that c-Raf may have anti-inflammatory and protective effects against LPS-stimulated ALI in mice.