Harnessing the Antiinflammatory Power of MyD88 to Reduce Allergic Fungal Inflammation?
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ABSTRACT:
SUBMITTER: Gaurav R
PROVIDER: S-EPMC7780992 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Previous studies indicate that soyasaponins may reduce inflammation via modulating toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling. However, its underlying mechanisms are still not fully understood. METHODS:Lipopolysaccharide (LPS)-challenged inflamed male ICR mice were intervened by intragastrical administration with 10 and 20??mol/kg·BW of soyasaponin A1, A2 or I for 8?weeks. The serum inflammatory markers were determined by commercial kits and the expression of molecules in TLR4/MyD88 signaling pathway in liver by real-time PCR and western blotting. The recruitments of TLR4 and MyD88 into lipid rafts of live tissue lysates were detected by sucrose gradient ultracentrifugation and western blotting. LPS-stimulated RAW264.7 macrophages were treated with 10, 20 and 40??mol/L of soyasaponin A1, A2 or I for 2?h. MyD88-overexpressed HEK293T cells were treated with 20 and 40??mol/L of soyasaponins (A1, A2 or I) or 20??mol/L of ST2825 (a MyD88 inhibitor) for 6?h. The expression of molecules in TLR4/MyD88 signaling pathway were determined by western blotting. Data were analyzed by using one way analysis of variance or t-test by SPSS 20.0 statistical software. RESULTS:Soyasaponins A1, A2 or I significantly reduced the levels of tumor necrosis factor alpha (TNF?), interleukin (IL)-6 and nitric oxide (NO) in serum (p?<?0.05), and decreased the mRNA levels of TNF?, IL-6, IL-1?, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) (p?<?0.05), the protein levels of myeloid differentiation protein 2 (MD-2), TLR4, MyD88, toll-interleukin1 receptor domain containing adaptor protein (TIRAP), phosphorylated interleukin-1 receptor-associated kinase 4 (p-IRAK-4), phosphorylated interleukin-1 receptor-associated kinase 1 (p-IRAK-1) and TNF receptor associated factor 6 (TRAF6) (p?<?0.05), and the recruitments of TLR4 and MyD88 into lipid rafts in liver (p?<?0.05). In LPS-stimulated macrophages, soyasaponins A2 or I significantly decreased MyD88 (p?<?0.05), soyasaponins A1, A2 or I reduced p-IRAK-4 and p-IRAK-1 (p?<?0.05), and soyasaponin I decreased TRAF6 (p?<?0.05). In MyD88-overexpressed HEK293T cells, soyasaponins (A1, A2 or I) and ST2825 significantly decreased MyD88 and TRAF6 (p?<?0.05). CONCLUSION:Soyasaponins can reduce inflammation by downregulating MyD88 expression and suppressing the recruitments of TLR4 and MyD88 into lipid rafts. This study provides novel understanding about the anti-inflammatory mechanism of soyasaponins.
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Project description:BackgroundIn our increasingly obesogenic environment, in which high-calorie convenience foods are readily available, food choices can drastically affect weight and overall health. Learned food preferences, which are developed through repeated pairings with positively and negatively valenced stimuli, can contribute to obesity susceptibility if positive attitudes toward high-calorie foods are developed. Thus, the modification of automatic associations with food may be a viable strategy to promote healthier eating behaviors.ObjectiveIn this study, we investigated the ability of an implicit priming (IP) intervention to alter responses to visual food cues by using an evaluative conditioning approach. The main objective was to implicitly (i.e., below conscious perception) associate disgust with high-calorie foods with the aim of reducing liking of these foods.DesignParticipants were randomly assigned to active or control IP. In active IP (n = 22), high-calorie food images were implicitly primed with negatively valenced images, and low-calorie food images were implicitly primed with positively valenced images. In control IP (n = 20), all food images were primed with neutral images of fixation crosses. Food images were rated on the desire to eat immediately before and after IP.ResultsA significant main effect of calorie (high compared with low; P < 0.001) and a significant calorie-by-group (active compared with control) interaction (P = 0.025) were observed. Post hoc tests identified a significantly greater high-calorie rating decline after active IP than after control IP (P = 0.036). Furthermore, there was significantly greater change in high-calorie ratings than in low-calorie ratings in the active group (P = 0.001). Active IP effects extended to high-calorie foods not specifically included in the intervention, which suggested an effect generalization. Moreover, a greater change in high-calorie ratings than in low-calorie ratings persisted 3-5 d after active IP (P < 0.007), which suggested lasting effects.ConclusionThis study provides initial evidence that IP can be used to alter high-calorie food preferences, which could promote healthier eating habits.
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Project description:Sensitization to fungi often leads to a severe form of asthma that is particularly difficult to manage clinically, resulting in increased morbidity and hospitalizations in these patients. Although B lymphocytes might exacerbate asthma symptoms through the production of IgE, these cells might also be important in the protective response against inhaled fungi. Through cytokine release and T-cell interactions, these lymphocytes might also influence the development and maintenance of airway wall fibrosis. J(H)(-/-) mice lack the JH gene for the heavy chain component of antibodies, which is critical for B-cell function and survival. These animals have facilitated the elucidation of the role of B lymphocytes in a number of immune responses; however, J(H)(-/-) mice have not been used to study fungal allergy. In this study, we examined the role of B lymphocytes using an Aspergillus fumigatus murine fungal aeroallergen model that mimics human airway disease that is triggered by environmental fungal exposure. We compared disease progression in sensitized wild-type BALB/c and J(H)(-/-) mice that were exposed to repeated fungal exposure and found no differences in airway hyperresponsiveness, overall pulmonary inflammation or collagen deposition around the large airways. However, the levels of the Th2-type cytokines IL-4 and IL-13 were significantly attenuated in the airways of J(H)(-/-) mice relative to the BALB/c controls. By contrast, levels of the inflammatory cytokines IL-17A and IL-6 were significantly elevated in the J(H)(-/-) animals, and there was significantly more robust airway eosinophilia and neutrophilia than in control animals. Taken together, these findings demonstrate that B lymphocytes help to regulate granulocytic responses to fungal exposure in the pulmonary compartment.
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2022-08-12 | GSE203483 | GEO