ABSTRACT
Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10+ M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10+ M2 macrophage production.
ABSTRACT
Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [18F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [18F]FBTA has a strong STING binding affinity (Kd = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [18F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [18F]fluorodeoxyglucose ([18F]FDG).
ABSTRACT
Objective:To study the positive expression rate of M2 subtype of macrophage cell surface molecules and the inflammatory factors of PPS in IL-4-induced M2 macrophage.Methods:The experiment was divided into 5 groups:blank control group, Model group,PPS groups(50 μg/ml,100 μg/ml and 200 μg/ml).The expression of CD206 and CD23 was used as bio-maker to confirm IL-4 induced macrophages by treating RAW264.7 with 20ng/ml of IL-4.IL-4 induced RAW264.7 cells were treated with PPS of 50μg/ml,100μg/ml and 200μg/ml for 24 h.Then the expression of CD206,CD16/32 and CD40 were analyzed by flow cytometry, and the mRNA expression of IL-1β,TNF-α,IL-10 and iNOS were detect by qRT-PCR.Results: After treated with IL-4,the positive rate of CD206 of RAW264.7 were high.After treated with PPS ,the rate of CD16/32 and CD40 in IL-4 induced RAW264.7 cells were high ,the expression of CD206 decreased,and the mRNA level of IL-1βand TNF-αincreased.Conclusion:RAW264.7 cells can be polarlized to M2 subtype macrophage by using 20 ng/ml IL-4.PPS enhances the mRNA of IL-1β,TNF-αand the expression of CD40, CD16/32 in IL-4-induced RAW264.7 cells .These results indicate that PPS can induce the M2 subtype to become M1 macrophages, can improve immune function of macrophages.