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Sheng Li Xue Bao : [Acta Physiologica... Jun 2024The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in...
The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1β levels in the hippocampus, increased serum IL-1β level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.
Topics: Animals; Receptors, Aryl Hydrocarbon; Male; Mice; Lipopolysaccharides; Depression; Mice, Inbred C57BL; Cytochrome P-450 CYP1A1; Hippocampus; Carbazoles; NLR Family, Pyrin Domain-Containing 3 Protein; Interleukin-1beta; Interleukin-6; Tumor Necrosis Factor-alpha; Behavior, Animal; Cytokines
PubMed: 38939930
DOI: No ID Found -
Frontiers in Cellular and Infection... 2024Recent studies have demonstrated a positive role of hyaluronic acid (HA) on periodontal clinical outcomes. This study aimed to investigate the impact of four different...
INTRODUCTION
Recent studies have demonstrated a positive role of hyaluronic acid (HA) on periodontal clinical outcomes. This study aimed to investigate the impact of four different HAs on interactions between periodontal biofilm and immune cells.
METHODS
The four HAs included: high-molecular-weight HA (HHA, non-cross-linked), low-molecular-weight HA (LHA), oligomers HA (OHA), and cross-linked high-molecular-weight HA (CHA). Serial experiments were conducted to verify the influence of HAs on: (i) 12-species periodontal biofilm (formation and pre-existing); (ii) expression of inflammatory cytokines and HA receptors in monocytic (MONO-MAC-6) cells and periodontal ligament fibroblasts (PDLF) with or without exposure to periodontal biofilms; (iii) generation of reactive oxygen species (ROS) in MONO-MAC-6 cells and PDLF with presence of biofilm and HA.
RESULTS
The results indicated that HHA and CHA reduced the bacterial counts in a newly formed (4-h) biofilm and in a pre-existing five-day-old biofilm. Without biofilm challenge, OHA triggered inflammatory reaction by increasing IL-1β and IL-10 levels in MONO-MAC cells and IL-8 in PDLF in a time-dependent manner, whereas CHA suppressed this response by inhibiting the expression of IL-10 in MONO-MAC cells and IL-8 in PDLF. Under biofilm challenge, HA decreased the expression of IL-1β (most decreasing HHA) and increased IL-10 levels in MONO-MAC-6 cells in a molecular weight dependent manner (most increasing CHA). The interaction between HA and both cells may occur via ICAM-1 receptor. Biofilm stimulus increased ROS levels in MONO-MAC-6 cells and PDLF, but only HHA slightly suppressed the high generation of ROS induced by biofilm stimulation in both cells.
CONCLUSION
Overall, these results indicate that OHA induces inflammation, while HHA and CHA exhibit anti-biofilm, primarily anti-inflammatory, and antioxidant properties in the periodontal environment.
Topics: Biofilms; Hyaluronic Acid; Humans; Reactive Oxygen Species; Fibroblasts; Cytokines; Monocytes; Periodontal Ligament; Cell Line; Interleukin-1beta; Interleukin-10
PubMed: 38938883
DOI: 10.3389/fcimb.2024.1414861 -
Immunity, Inflammation and Disease Jun 2024To explore the efficacy and potential mechanism of Fengshi Gutong capsule (FSGTC) in osteoarthritis (OA) inflammation.
OBJECTIVE
To explore the efficacy and potential mechanism of Fengshi Gutong capsule (FSGTC) in osteoarthritis (OA) inflammation.
METHODS
The impact of FSGTC on laboratory indicators of OA patients was explored using data mining technology and association rule analysis. Then, the OA cell model was constructed by inducing chondrocytes (CHs) with interleukin-1β (IL-1β). In the presence of FSGTC intervention, the regulatory mechanism of PACER/COX2/PGE2 in OA-CH viability and inflammatory responses was evaluated.
RESULTS
Retrospective data mining showed that FSGTC effectively reduced inflammation indexes (ESR, HCRP) of OA patients. Cell experiments showed that LncRNA PACER (PACER) silencing inhibited the proliferation activity of OA-CHs, increased the level of COX2 protein, elevated the levels of PGE2, TNF-α, and IL-1β, and decreased the levels of IL-4 and IL-10 (p < .01). On the contrary, FSGTC-containing serum reversed the effect of PACER silencing on OA-CHs (p < .01). After the addition of COX2 pathway inhibitor, the proliferation activity of OA-CHs was enhanced; the levels of PGE2, TNF-α, and IL-1β were decreased while the levels of IL-4 and IL-10 were increased (p < .01).
CONCLUSION
FSGTC inhibits IL-1β-induced inflammation in CHs and ameliorates OA by upregulating PACER and downregulating COX2/PGE2.
Topics: Chondrocytes; RNA, Long Noncoding; Humans; Interleukin-1beta; Cyclooxygenase 2; Dinoprostone; Osteoarthritis; Inflammation; Drugs, Chinese Herbal; Down-Regulation; Male; Female; Up-Regulation; Middle Aged
PubMed: 38938021
DOI: 10.1002/iid3.1334 -
Scientific Reports Jun 2024There is no treatment for acute aortic dissection (AAD) targeting inflammatory cells. We aimed to identify the new therapeutic targets associated with inflammatory...
There is no treatment for acute aortic dissection (AAD) targeting inflammatory cells. We aimed to identify the new therapeutic targets associated with inflammatory cells. We characterized the specific distribution of myeloid cells of both human type A AAD samples and a murine AAD model generated using angiotensin II (ANGII) and β-aminopropionitrile (BAPN) by single-cell RNA sequencing (scRNA-seq). We also examined the effect of an anti-interleukin-1β (IL-1β) antibody in the murine AAD model. IL1B inflammatory macrophages and classical monocytes were increased in human AAD samples. Trajectory analysis demonstrated that IL1B inflammatory macrophages differentiated from S100A8/9/12 classical monocytes uniquely observed in the aorta of AAD. We found increased infiltration of neutrophils and monocytes with the expression of inflammatory cytokines in the aorta and accumulation of inflammatory macrophages before the onset of macroscopic AAD in the murine AAD model. In blocking experiments using an anti-IL-1β antibody, it improved survival of murine AAD model by preventing elastin degradation. We observed the accumulation of inflammatory macrophages expressing IL-1β in both human AAD samples and in a murine AAD model. Anti-IL-1β antibody could improve the mortality rate in mice, suggesting that it may be a treatment option for AAD.
Topics: Aortic Dissection; Interleukin-1beta; Animals; Humans; Macrophages; Mice; Disease Models, Animal; Male; Aminopropionitrile; Angiotensin II; Inflammation; Monocytes; Aorta; Mice, Inbred C57BL; Female
PubMed: 38937528
DOI: 10.1038/s41598-024-65931-3 -
PloS One 2024We investigated the interactions of unopsonized and opsonized Mycoplasma mycoides subsp. mycoides (Mmm) with bovine macrophages in vitro. Mmm survived and proliferated...
We investigated the interactions of unopsonized and opsonized Mycoplasma mycoides subsp. mycoides (Mmm) with bovine macrophages in vitro. Mmm survived and proliferated extracellularly on bovine macrophage cell layers in the absence of Mmm-specific antisera. Bovine complement used at non-bactericidal concentrations did neither have opsonizing effect nor promoted intracellular survival, whereas Mmm-specific antisera substantially increased phagocytosis and Mmm killing. A phagocytosis-independent uptake of Mmm by macrophages occurred at a high multiplicity of infection, also found to induce the production of TNF, and both responses were unaffected by non-bactericidal doses of bovine complement. Bovine complement used at higher doses killed Mmm in cell-free cultures and completely abrogated TNF responses by macrophages. These results provide a framework to identify Mmm antigens involved in interactions with macrophages and targeted by potentially protective antibodies and point towards a pivotal role of complement in the control of inflammatory responses in contagious bovine pleuropneumonia.
Topics: Animals; Cattle; Macrophages; Phagocytosis; Complement System Proteins; Mycoplasma; Tumor Necrosis Factor-alpha; Pleuropneumonia, Contagious; Mycoplasma mycoides
PubMed: 38935768
DOI: 10.1371/journal.pone.0305851 -
Blood Jun 2024
Topics: Humans; Interleukin-1
PubMed: 38935360
DOI: 10.1182/blood.2024024648 -
Nutrients Jun 2024Corn peptide (CP) is a short, naturally occurring, and physiologically active peptide generated from corn-protease-catalyzed hydrolysis. CP plays a role in preventing...
Corn peptide (CP) is a short, naturally occurring, and physiologically active peptide generated from corn-protease-catalyzed hydrolysis. CP plays a role in preventing obesity-related disorders, but its impact on reducing inflammation is unknown. Hence, this study examined the possible protective effects of corn peptide powder (CPP) against the harmful effects of lipopolysaccharide (LPS), with a particular emphasis on reducing oxidative damage and inflammation in adipocytes. Hence, mature 3T3-L1 adipocytes underwent exposure to 10 ng/mL LPS, with or without CPP (10 and 20 μg/mL). LPS stimulation increased reactive oxygen species and superoxide anion generation. However, this effect was reduced in a dose-dependent manner by pretreatment with CPP. CPP treatment elevated the mRNA expressions of the antioxidant enzymes manganese superoxide dismutase (mnSOD) and glutathione peroxidase 1 (Gpx1) while reducing the mRNA expressions of the cytosolic reactive oxygen species indicators p40 and p67 (NADPH oxidase 2). In addition, CPP inhibited the monocyte chemoattractant protein-1, tumor necrosis factor-alpha, Toll-like receptor 4, and nuclear factor kappa B mRNA expressions induced by LPS. These findings demonstrate that CPP may ameliorate adipocyte dysfunction by suppressing oxidative damage and inflammatory responses through a new mechanism known as Toll-like receptor 4/nuclear factor kappa B-mediated signaling.
Topics: Animals; Mice; 3T3-L1 Cells; Adipocytes; Lipopolysaccharides; Zea mays; Reactive Oxygen Species; Inflammation; Toll-Like Receptor 4; Oxidative Stress; Superoxide Dismutase; Powders; Peptides; Glutathione Peroxidase; NF-kappa B; Antioxidants; Glutathione Peroxidase GPX1; Signal Transduction; Chemokine CCL2; Tumor Necrosis Factor-alpha; Anti-Inflammatory Agents
PubMed: 38931278
DOI: 10.3390/nu16121924 -
Nutrients Jun 2024The hawthorn fruit is an interesting medicinal plant that has several biological features, especially related to anti-inflammatory, antioxidant and immune-modulating...
The hawthorn fruit is an interesting medicinal plant that has several biological features, especially related to anti-inflammatory, antioxidant and immune-modulating actions, and boosting general health. In this study, we aimed to clarify the immunological effects of hawthorn vinegar on immunity and general health. We also focused on three different production processes to improve the antioxidant activity of hawthorn vinegar (2) Methods: In the study, besides the traditional production of hawthorn vinegar (N), thermal pasteurization (P) and ultrasound (U) techniques were applied to vinegars. A total of 56 female adult Wistar albino rats were randomly allocated into seven groups; Control, N0.5 (regular vinegar; 0.5 mL/kgbw), N1 (regular vinegar; 1 mL/kgbw), P0.5 (pasteurized vinegar; 0.5 mL/kgbw), P1 (pasteurized vinegar; 1 mL/kgbw), U0.5 (ultrasound treated vinegar; 0.5 mL/kgbw), and U1 (ultrasound treated vinegar; 1 mL/kgbw). Vinegars were administered by oral gavage daily. The average weight gains, body mass index, and blood hematological parameters were measured, and the Neutrophil Lymphocyte ratio was calculated. The plasma IL-1β and TNF-α values, and MDA, IL-1β and TNF-α values of intestinal tissue, were determined. Also, the streptavidin-biotin-peroxidase complex method was applied to determine the expressions of TNF-α and IL-1β in duodenum. (3) Results: There was a decreasing tendency in the average weight gains in all vinegar groups compared to the control group. In addition, there was an increase in NL ratio in all vinegar groups, although not significant. There were no statistical differences among all vinegar groups, although decreases were observed in plasma IL-1β. Also, the plasma TNF-α values showed slight increases in high-dose-of-vinegar groups (N1, P1 and U1), although not significant. In addition, the intestinal tissue IL-1β value tended to increase in groups N0.5, N1 and P0.5, while it tended to decrease in P1, U0.5 and U1. On the other hand, there were slight increases in the TNF-α values of intestinal tissue in all groups compared to control, although these were not significant. Furthermore, the intensive expressions of TNF-α and IL-1β were determined in groups U0.5 and U1. (4) Conclusions: The results suggest that either high doses or ultrasound applications of hawthorn vinegar have positive effects on intestinal health, boosting immunity and general health.
Topics: Animals; Female; Acetic Acid; Rats, Wistar; Crataegus; Rats; Antioxidants; Interleukin-1beta; Tumor Necrosis Factor-alpha; Fruit
PubMed: 38931223
DOI: 10.3390/nu16121868 -
Molecules (Basel, Switzerland) Jun 2024Seven new abietane diterpenoids, comprising medusanthol A-G (-, , -) and two previously identified analogs ( and ), were isolated from the hexane extract of the aerial...
Seven new abietane diterpenoids, comprising medusanthol A-G (-, , -) and two previously identified analogs ( and ), were isolated from the hexane extract of the aerial parts of The structures of the compounds were elucidated by HRESIMS, 1D/2D NMR spectroscopic data, IR spectroscopy, NMR calculations with DP4+ probability analysis, and ECD calculations. The anti-neuroinflammatory potential of compounds - was evaluated by determining their ability to inhibit the production of nitric oxide (NO) and the proinflammatory cytokine TNF-α in BV2 microglia stimulated with LPS and IFN-γ. Compounds - and exhibited decreased NO levels at a concentration of 12.5 µM. Compound demonstrated strong activity with an IC of 3.12 µM, and compound had an IC of 15.53 µM; both compounds effectively reduced NO levels compared to the positive control quercetin (IC 11.8 µM). Additionally, both compounds significantly decreased TNF-α levels, indicating their potential as promising anti-neuroinflammatory agents.
Topics: Abietanes; Anti-Inflammatory Agents; Animals; Nitric Oxide; Mice; Microglia; Tumor Necrosis Factor-alpha; Plant Extracts; Cell Line; Molecular Structure; Lipopolysaccharides; Plant Components, Aerial
PubMed: 38930790
DOI: 10.3390/molecules29122723 -
International Journal of Molecular... Jun 2024Extensive evidence supports the connection between obesity-induced inflammation and the heightened expression of IL-6 adipose tissues. However, the mechanism underlying...
Extensive evidence supports the connection between obesity-induced inflammation and the heightened expression of IL-6 adipose tissues. However, the mechanism underlying the IL-6 exacerbation in the adipose tissue remains unclear. There is general agreement that TNF-α and stearate concentrations are mildly elevated in adipose tissue in the state of obesity. We hypothesize that TNF-α and stearate co-treatment induce the increased expression of IL-6 in mouse adipocytes. We therefore aimed to determine IL-6 gene expression and protein production by TNF-α/stearate treated adipocytes and investigated the mechanism involved. To test our hypothesis, 3T3-L1 mouse preadipocytes were treated with TNF-α, stearate, or TNF-α/stearate. IL-6 gene expression was assessed by quantitative real-time qPCR. IL-6 protein production secreted in the cell culture media was determined by ELISA. Acetylation of histone was analyzed by Western blotting. Il6 region-associated histone H3 lysine 9/18 acetylation (H3K9/18Ac) was determined by ChIP-qPCR. 3T3-L1 mouse preadipocytes were co-challenged with TNF-α and stearate for 24 h, which led to significantly increased IL-6 gene expression (81 ± 2.1 Fold) compared to controls stimulated with either TNF-α (38 ± 0.5 Fold; = 0.002) or stearate (56 ± 2.0 Fold; = 0.013). As expected, co-treatment of adipocytes with TNF-α and stearate significantly increased protein production (338 ± 11 pg/mL) compared to controls stimulated with either TNF-α (28 ± 0.60 pg/mL; = 0.001) or stearate (53 ± 0.20 pg/mL, = 0.0015). Inhibition of histone acetyltransferases (HATs) with anacardic acid or curcumin significantly reduced the IL-6 gene expression and protein production by adipocytes. Conversely, TSA-induced acetylation substituted the stimulatory effect of TNF-α or stearate in their synergistic interaction for driving IL-6 gene expression and protein production. Mechanistically, TNF-α/stearate co-stimulation increased the promoter-associated histone H3 lysine 9/18 acetylation (H3K9/18Ac), rendering a transcriptionally permissive state that favored IL-6 expression at the transcriptional and translational levels. Our data represent a TNF-α/stearate cooperativity model driving IL-6 expression in 3T3-L1 cells via the H3K9/18Ac-dependent mechanism, with implications for adipose IL-6 exacerbations in obesity.
Topics: Animals; Mice; Histones; Interleukin-6; 3T3-L1 Cells; Tumor Necrosis Factor-alpha; Acetylation; Adipocytes; Stearic Acids; Gene Expression Regulation
PubMed: 38928498
DOI: 10.3390/ijms25126776