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Journal of Natural Medicines Jun 2021The anti-inflammatory effects of a 50% aqueous extract of Rosa roxburghii fruit (RRFE) and two ellagitannins (strictinin and casuarictin) isolated from the RRFE were...
The anti-inflammatory effects of a 50% aqueous extract of Rosa roxburghii fruit (RRFE) and two ellagitannins (strictinin and casuarictin) isolated from the RRFE were evaluated in a cell model of skin inflammation induced by self-RNA released from epidermal cells damaged by UV ray (UVR) irradiation. The RRFE inhibited interleukin-8 (IL-8) mRNA expression in normal human epidermal keratinocytes (NHEKs) stimulated with polyinosinic:polycytidylic acid (poly(I:C)), a ligand of toll-like receptor-3 (TLR-3). The plant-derived anti-inflammatory agents, dipotassium glycyrrhizinate (GK2) and allantoin, had no influence on the IL-8 expression. The purified compounds, strictinin and casuarictin, inhibited the IL-8 mRNA expression and IL-8 release induced in NHEKs by poly(I:C). These ellagitannins were thus found to be responsible for the biological activity exhibited by the RRFE. This study demonstrates that RRFE and isolated RRFE compounds show promise as ingredients for products formulated to improve skin disorders induced by UVR irradiation.
Topics: Biphenyl Compounds; Cells, Cultured; Fruit; Gallic Acid; Humans; Hydrolyzable Tannins; Interleukin-8; Keratinocytes; Phenols; Poly I-C; Rosa; Ultraviolet Rays
PubMed: 33830449
DOI: 10.1007/s11418-021-01509-x -
Fish & Shellfish Immunology Sep 2022Cathepsins are major lysosomal enzymes that participate in necessary physiological processes, including protein degradation, tissue differentiation, and innate or...
Cathepsins are major lysosomal enzymes that participate in necessary physiological processes, including protein degradation, tissue differentiation, and innate or adaptive immune responses. According to their proteolytic activity, vertebrate cathepsins are classified as cysteine proteases (cathepsins B, C, F, H, K, L, O, S, V, W, and X or Z), aspartic proteases (cathepsin D and E), and serine proteases (cathepsin A and G). Several cathepsins were reported in teleosts, however, no cathepsin gene has been identified from Pacific cod so far. In the present study, a total of 13 cathepsin genes were identified for Pacific cod. The evolutionary path of each cathepsin gene was demonstrated via analysis of phylogenetic trees, multiple alignments, conserved domains, motif compositions, and tertiary structures. Tissue distribution analysis showed that all cathepsin genes were ubiquitously expressed in eight healthy tissues but they exhibited diverse levels of expression. Several cathepsin genes were found to be highly expressed in the kidney, spleen, head kidney and liver, whereas low or modest levels were detected in the gills, skin, intestines, and heart. Temporal-specific expression of cathepsins in early developmental stages of Pacific cod were also conducted. CTSK, S, F, and Z were highly expressed at 1 dph and 5 dph and decreased later, while CTSL, L1, and L.1 transcript levels gradually increased in a time-dependent manner. Additionally, the expression profiles of cathepsin genes in Pacific cod were evaluated in the spleen and liver after poly I:C challenge. The results indicated that all cathepsin genes were significantly upregulated upon poly I:C stimulation, suggesting that they play key roles in antiviral immune responses in Pacific cod. Our findings establish a foundation for future exploration of the molecular mechanisms of cathepsins in modulating antiviral immunity in Pacific cod.
Topics: Animals; Antiviral Agents; Cathepsin A; Cathepsin B; Cathepsin D; Cathepsin L; Cathepsins; Gadiformes; Phylogeny; Poly I-C
PubMed: 35985629
DOI: 10.1016/j.fsi.2022.08.025 -
Scientific Reports May 2023Most individuals with neurodevelopmental disorders (NDDs), including schizophrenia and autism spectrum disorders, experience disruptions in sleep and circadian rhythms....
Most individuals with neurodevelopmental disorders (NDDs), including schizophrenia and autism spectrum disorders, experience disruptions in sleep and circadian rhythms. Epidemiological studies indicate that exposure to prenatal infection increases the risk of developing NDDs. We studied how environmental circadian disruption contributes to NDDs using maternal immune activation (MIA) in mice, which models prenatal infection. Pregnant dams were injected with viral mimetic poly IC (or saline) at E9.5. Adult poly IC- and saline-exposed offspring were subjected to 4 weeks of each of the following: standard lighting (LD1), constant light (LL) and standard lighting again (LD2). Behavioral tests were conducted in the last 12 days of each condition. Poly IC exposure led to significant behavioral differences, including reduced sociability (males only) and deficits in prepulse inhibition. Interestingly, poly IC exposure led to reduced sociability specifically when males were tested after LL exposure. Mice were exposed again to either LD or LL for 4 weeks and microglia were characterized. Notably, poly IC exposure led to increased microglial morphology index and density in dentate gyrus, an effect attenuated by LL exposure. Our findings highlight interactions between circadian disruption and prenatal infection, which has implications in informing the development of circadian-based therapies for individuals with NDDs.
Topics: Pregnancy; Female; Male; Humans; Mice; Animals; Prenatal Exposure Delayed Effects; Poly I-C; Prepulse Inhibition; Schizophrenia; Behavior, Animal; Disease Models, Animal
PubMed: 37179433
DOI: 10.1038/s41598-023-34363-w -
Brain, Behavior, and Immunity Jul 2021Environmental enrichment (EE) has been successfully implemented in human rehabilitation settings. However, the mechanisms underlying its success are not understood....
Environmental enrichment (EE) has been successfully implemented in human rehabilitation settings. However, the mechanisms underlying its success are not understood. Incorporating components of EE protocols into our animal models allows for the exploration of these mechanisms and their role in mitigation. Using a mouse model of maternal immune activation (MIA), the present study explored disruptions in social behavior and associated hypothalamic pituitary adrenal (HPA) axis functioning, and whether a supportive environment could prevent these effects. We show that prenatal immune activation of toll-like receptor 3, by the viral mimetic polyinosinic-polycytidylic acid (poly(I:C)), led to disrupted maternal care in that dams built poorer quality nests, an effect corrected by EE housing. Standard housed male and female MIA mice engaged in higher rates of repetitive rearing and had lower levels of social interaction, alongside sex-specific expression of several ventral hippocampal neural stress markers. Moreover, MIA males had delayed recovery of plasma corticosterone in response to a novel social encounter. Enrichment housing, likely mediated by improved maternal care, protected against these MIA-induced effects. We also evaluated c-Fos immunoreactivity associated with the novel social experience and found MIA to decrease neural activation in the dentate gyrus. Activation in the hypothalamus was blunted in EE housed animals, suggesting that the putative circuits modulating social behaviors may be different between standard and complex housing environments. These data demonstrate that augmentation of the environment supports parental care and offspring safety/security, which can offset effects of early health adversity by buffering HPA axis dysregulation. Our findings provide further evidence for the viability of EE interventions in maternal and pediatric settings.
Topics: Animals; Child; Female; Hippocampus; Humans; Hypothalamo-Hypophyseal System; Male; Pituitary-Adrenal System; Poly I-C; Pregnancy; Prenatal Exposure Delayed Effects; Social Behavior
PubMed: 33766701
DOI: 10.1016/j.bbi.2021.03.018 -
Biomolecules May 2022The ventral tegmental area (VTA) in the ventral midbrain is the origin of the dopaminergic neurotransmission pathways. Although GABA receptors and AKT-GSK3β signaling...
The ventral tegmental area (VTA) in the ventral midbrain is the origin of the dopaminergic neurotransmission pathways. Although GABA receptors and AKT-GSK3β signaling are involved in the pathophysiology of mental disorders and are modulated by antipsychotics, an unmet task is to reveal the pathological changes in these biomarkers and antipsychotic modulations in the VTA. Using a juvenile polyriboinosinic-polyribocytidylic acid (Poly I:C) psychiatric rat model, this study investigated the effects of adolescent risperidone treatment on GABA receptors and AKT/GSK3β in the VTA. Pregnant female Sprague-Dawley rats were administered Poly I:C (5mg/kg; i.p) or saline at gestational day 15. Juvenile female offspring received risperidone (0.9 mg/kg, twice per day) or a vehicle from postnatal day 35 for 25 days. Poly I:C offspring had significantly decreased mRNA expression of GABA receptor β3 subunits and glutamic acid decarboxylase (GAD2) in the VTA, while risperidone partially reversed the decreased GAD2 expression. Prenatal Poly I:C exposure led to increased expression of AKT2 and GSK3β. Risperidone decreased GABA receptor β2/3, but increased AKT2 mRNA expression in the VTA of healthy rats. This study suggests that Poly I:C-elicited maternal immune activation and risperidone differentially modulate GABAergic neurotransmission and AKT-GSK3β signaling in the VTA of adolescent rats.
Topics: Animals; Antipsychotic Agents; Female; Glycogen Synthase Kinase 3 beta; Humans; Poly I-C; Pregnancy; Proto-Oncogene Proteins c-akt; RNA, Messenger; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; Risperidone; Ventral Tegmental Area; gamma-Aminobutyric Acid
PubMed: 35625659
DOI: 10.3390/biom12050732 -
Advanced Science (Weinheim,... Nov 2023The efficient activation of professional antigen-presenting cells-such as dendritic cells (DC)-in tumors and lymph nodes is critical for the design of next-generation...
The efficient activation of professional antigen-presenting cells-such as dendritic cells (DC)-in tumors and lymph nodes is critical for the design of next-generation cancer vaccines and may be able to provide anti-tumor effects by itself through immune stimulation. The challenge is to stimulate these cells without causing excessive toxicity. It is hypothesized that a multi-pronged combinatorial approach to DC stimulation would allow dose reductions of innate immune receptor-stimulating TLR3 agonists while enhancing drug efficacy. Here, a hybrid lipid nanoparticle (LNP) platform is developed and tested for double-stranded RNA (polyinosinic:polycytidylic acid for TLR3 agonism) and immune modulator (L-CANDI) delivery. This study shows that the ≈120 nm hybrid nanoparticles-in-nanoparticles effectively eradicate tumors by themselves and generate long-lasting, durable anti-tumor immunity in mouse models.
Topics: Animals; Mice; Toll-Like Receptor 3; Poly I-C; Cancer Vaccines; Neoplasms; Dendritic Cells
PubMed: 37814359
DOI: 10.1002/advs.202303576 -
Frontiers in Immunology 2023Viral pneumonia is a global health burden with a high mortality rate, especially in the elderly and in patients with underlying diseases. Recent studies have found that...
Viral pneumonia is a global health burden with a high mortality rate, especially in the elderly and in patients with underlying diseases. Recent studies have found that myeloid-derived suppressor cells (MDSCs) are abundant in these patient groups; however, their roles in the progression of viral pneumonia remain unclear. In this study, we observed a substantial increase in MDSCs in a mouse model of renal ischemia/reperfusion (I/R) injury and in older mice. When intranasal polyinosinic-polycytidylic acid (poly(I:C)) administration was used to mimic viral pneumonia, mice with renal I/R injury exhibited more severe lung inflammation than sham mice challenged with poly(I:C). In addition, MDSC depletion attenuated lung inflammation in mice with I/R injury. Similar results were obtained in older mice compared with those in young mice. Furthermore, adoptive transfer of in -differentiated MDSCs exacerbated poly(I:C)-induced lung inflammation. Taken together, these experimental results suggest that the increased proportion of MDSCs in mice with renal I/R injury and in older mice exacerbates poly(I:C)-induced lung inflammation. These findings have important implications for the treatment and prevention of severe lung inflammation caused by viral pneumonia.
Topics: Humans; Mice; Animals; Aged; Myeloid-Derived Suppressor Cells; Poly I-C; Kidney; Disease Models, Animal; Pneumonia, Viral
PubMed: 37818369
DOI: 10.3389/fimmu.2023.1243851 -
Cells Feb 2020Schizophrenia is a complex psychiatric disorder that exhibits an interconnection between the immune system and the brain. Experimental and clinical studies have...
Schizophrenia is a complex psychiatric disorder that exhibits an interconnection between the immune system and the brain. Experimental and clinical studies have suggested the presence of neuroinflammation in schizophrenia. In the present study, the effect of antipsychotic drugs, including clozapine, risperidone, and haloperidol (10, 20 and 20 μM, respectively), on the production of IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, IL-18, INF-γ, and TNF-α was investigated in the unstimulated and polyriboinosinic-polyribocytidilic acid [poly (I:C)]-stimulated primary microglial cell cultures. In the unstimulated cultures, clozapine, risperidone, and haloperidol did not influence the cytokine levels. Nevertheless, in cell cultures under strong inflammatory activation by poly (I:C), clozapine reduced the levels of IL-1α, IL-1β, IL-2, and IL-17. Risperidone and haloperidol both reduced the levels of IL-1α, IL-1β, IL-2, and IL-17, and increased the levels of IL-6, IL-10, INF-γ, and TNF-α. Based on the results that were obtained with the antipsychotic drugs and observing that clozapine presented with a more significant anti-inflammatory effect, clozapine was selected for the subsequent experiments. We compared the profile of cytokine suppression obtained with the use of NLRP3 inflammasome inhibitor, CRID3 to that obtained with clozapine, to test our hypothesis that clozapine inhibits the NLRP3 inflammasome. Clozapine and CRID3 both reduced the IL-1α, IL-1β, IL-2, and IL-17 levels. Clozapine reduced the level of poly (I:C)-activated NLRP3 expression by 57%, which was higher than the reduction thay was seen with CRID3 treatment (45%). These results suggest that clozapine might exhibit anti-inflammatory effects by inhibiting NLRP3 inflammasome and this activity is not typical with the use of other antipsychotic drugs under the conditions of strong microglial activation.
Topics: Animals; Antipsychotic Agents; Clozapine; Drug Interactions; Female; Humans; Inflammasomes; Inflammation; Male; Mice; Microglia; NLR Family, Pyrin Domain-Containing 3 Protein; Poly I-C; Pregnancy; Primary Cell Culture; Rats; Schizophrenia; Signal Transduction
PubMed: 32121312
DOI: 10.3390/cells9030577 -
MBio Mar 2020Viral diseases cause significant losses in aquaculture. Prophylactic measures, such as immune priming, are promising control strategies. Treatment of the Pacific oyster...
Viral diseases cause significant losses in aquaculture. Prophylactic measures, such as immune priming, are promising control strategies. Treatment of the Pacific oyster () with the double-stranded RNA analog poly(I·C) confers long-term protection against infection with ostreid herpesvirus 1, the causative agent of Pacific oyster mortality syndrome. In a recent article in , Lafont and coauthors (M. Lafont, A. Vergnes, J. Vidal-Dupiol, J. de Lorgeril, et al., mBio 11:e02777-19, 2020, https://doi.org/10.1128/mBio.02777-19) characterized the transcriptome of oysters treated with poly(I·C). This immune stimulator induced genes related to the interferon and apoptosis pathways. This response overlaps the response to viral infection, and high expression levels of potential effector genes are maintained for up to 4 months. This work opens the door to characterization of the phenomena of immune priming in a poorly studied invertebrate model. It also highlights the importance of interferon-like responses for invertebrate antiviral immunity.
Topics: Animals; Antiviral Agents; Crassostrea; Poly I-C; RNA, Double-Stranded
PubMed: 32209685
DOI: 10.1128/mBio.00407-20 -
Journal of Controlled Release :... Mar 2022Adjuvant loaded nanoparticles are a potent strategy for developing effective combined cancer immunotherapies. A polyinosinic-polycytidylic acid (poly I:C) is a ligand...
Adjuvant loaded nanoparticles are a potent strategy for developing effective combined cancer immunotherapies. A polyinosinic-polycytidylic acid (poly I:C) is a ligand for toll-like receptor 3 and a promising cancer adjuvant. However, regarding intravenous administration, the potential for and the mechanism of poly I:C loaded nanoparticles as a cancer vaccine are largely unknown. We investigated the effects of using a combination of poly I:C and an antigen loaded liposome for cancer immunotherapy and a key process for achieving effective antitumor immunity of the liposome system under conditions of intravenous vaccination. A poly I:C and ovalbumin (OVA) loaded octaarginine (R8) modified liposome (PoIC/OVA-R8L) drastically inhibited the systemic cytokine production derived from the poly I:C intravenous injection. Treatment with PoIC/OVA-R8L improved the immune status in B16-OVA tumors to an inflamed immune status and induced a significant combined antitumor effect with the anti-programmed cell death 1 ligand (PD-L1). In a mechanistic analysis compared with a high dose of the free form of poly I:C, interestingly, local cytokine production, maturation of antigen presenting cells and antigen presentation were comparable. Conversely, significant differences were identified in the processes after OVA-specific CTL generation. Collectively, our findings have implications for the development of intravenous liposomal vaccines.
Topics: Adjuvants, Immunologic; Administration, Intravenous; Animals; Antigen Presentation; Cancer Vaccines; Cytokines; Dendritic Cells; Ligands; Liposomes; Mice; Mice, Inbred C57BL; Neoplasms; Ovalbumin; Poly I-C
PubMed: 35065157
DOI: 10.1016/j.jconrel.2022.01.020