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1.
J Cell Physiol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31674024

RESUMO

Endometritis is an inflammatory change in the structure of the endometrium due to various causes and is a common cause of infertility. Studies have confirmed that microRNAs (miRNAs) play a key regulatory role in various inflammatory diseases. However, the miRNA-mediated mechanism of endometrial inflammation induced by lipopolysaccharides (LPS) remains unclear. In this study, real-time quantitative polymerase chain reaction, Western blot analysis, immunofluorescence and Rac family small GTPase 1 (Rac1) interference were used to reveal the overexpression of miR-488 in the LPS-induced bovine uterus, and the effect of protein kinase B κ-light chain enhancement of the nuclear factor-activated B cells (AKT/NF-κB) pathway in intimal epithelial cells. The results showed that the expression of inflammatory cytokines such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α in the experimental group was significantly lower than that in the control group when miR-488 was overexpressed. Similar results were observed in the expression levels of p-AKT, p-IKK, and p-p65 proteins. In addition, the dual-luciferase reporter system confirmed that miRNA-488 may directly target the 3'-untranslated region of Rac1. In turn, the expression of Rac1 was inhibited. Moreover, the nuclear translocation of NF-κB was inhibited, and meanwhile, the accumulation of reactive oxygen species (ROS) in the cells was reduced. Thus, we provide basic data for the negative regulation of miR-488 in LPS-induced inflammation by inhibiting ROS production and the AKT/NF-kB pathway in intimal epithelial cells.

2.
Int J Biol Sci ; 15(11): 2308-2319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595149

RESUMO

Acute lung injury (ALI) is a common clinical disease with high incidence and mortality rate, which is characterized by severe inflammatory response and tissues damage. MicroRNAs (miRNAs) have been regarded as novel regulators of inflammation, and play an important role in various inflammatory diseases. However, it remains unknown whether the regulatory mechanisms mediated by miR-106a is involved in LPS-induced ALI. In this study, we found that expression of miR-106a was significantly decreased in lung tissues of ALI mice and LPS-stimulated macrophages. We also revealed that over-expression of miR-106a significantly decreased the production of pro-inflammatory cytokines, including IL-1ß, IL-6 and TNF-α, whereas this effect was reversed by the inhibition of miR-106a. Moreover, miR-106a inhibits NF-κB activation by targeting TLR4 expression. We further demonstrated that miR-106a inhibited TLR4 expression via binding directly to the 3'-UTR of TLR4. Taken together, the results of the present study illuminated that miR-106a is a negative feedback regulator in LPS-stimulated inflammation through TLR4/NF-κB signaling pathway.

3.
Microb Pathog ; 137: 103767, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31580956

RESUMO

Acute lung inflammation is one among the top of infectious diseases. It is a pulmonary dysfunctional disease. It breaks the physiological coordination in the structures and functions of respiratory system. There are a few effective treatments to minimize the mortality of acute lung inflammation. It was induced by Staphylococcus aureus (S. aureus) via nasal instillation of mice. The common ivy (Hedera helix) is the most significant medicinal plant and considered as a traditional medicinal plant. The most active ingredient in the extract of ivy plant was Hederacoside-C (HDC). The purpose of this study was to investigate its anti-inflammatory effects on induced acute lung inflammation in vivo and (RAW 264.7 cells) in vitro and to elucidate its anti-inflammatory mechanisms. HDC was administered intraperitoneally 1 h after infection until 24 h. The dose was repeated every 8 h for three successful doses. Mice treated with HDC significantly reduced the pulmonary edema, white blood cells, wet-dry ratio (W/D) and myeloperoxidase (MPO) activity. HDC attenuated protein expression levels of MAPKs including p38, ERK, JNK and NF-κB including p65 and IκB-α pathways analyzed by ELISA. HDC also suppressed the protein expressions of TLR2 & TLR4 detected by Western blot. HDC also downregulated the gene expression of pro-inflammatory cytokines including IL-6, IL-1ß and TNF-α, but upregulated the gene expression of an anti-inflammatory cytokine IL-10 analyzed by qRT-PCR. In conclusion, our results stated that HDC could inhibit the S. aureus induced acute lung inflammation and it may be a potential therapeutic drug against acute lung inflammation.

4.
J Cell Physiol ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541458

RESUMO

Breast cancer is a common malignancy that is highly lethal with poor survival rates and immature therapeutics that urgently needs more effective and efficient therapies. MicroRNAs are intrinsically involved in different cancer remedies, but their mechanism in breast cancer has not been elucidated for prospective treatment. The function and mechanism of microRNA-188-5p (miR-188) have not been thoroughly investigated in breast cancer. In our study, we found that the expression of miR-188 in breast cancer tissues was obviously reduced. Our findings also revealed the abnormal overexpression of miR-188 in 4T1 and MCF-7 cells significantly suppressed cell proliferation and migration and also enhanced apoptosis. miR-188 induced cell cycle arrest in the G1 phase. To illuminate the molecular mechanism of miR-188, Rap2c was screened as a single target gene by bioinformatics database analysis and was further confirmed by dual-luciferase assay. Moreover, Rap2c was found to be a vital molecular switch for the mitogen-activated protein kinase signaling pathway in tumor progression by decreasing apoptosis and promoting proliferation and migration. In conclusion, our results revealed that miR-188 is a cancer progression suppressor and a promising future target for breast cancer therapy.

5.
J Zhejiang Univ Sci B ; 20(10): 816-827, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31489801

RESUMO

Catalpol is the main active ingredient of an extract from Radix rehmanniae, which in a previous study showed a protective effect against various types of tissue injury. However, a protective effect of catalpol on uterine inflammation has not been reported. In this study, to investigate the protective mechanism of catalpol on lipopolysaccharide (LPS)-induced bovine endometrial epithelial cells (bEECs) and mouse endometritis, in vitro and in vivo inflammation models were established. The Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway and its downstream inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), western blot (WB), and immunofluorescence techniques. The results from ELISA and qRT-PCR showed that catalpol dose-dependently reduced the expression of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1ß, and IL-6, and chemokines such as C-X-C motif chemokine ligand 8 (CXCL8) and CXCL5, both in bEECs and in uterine tissue. From the experimental results of WB, qRT-PCR, and immunofluorescence, the expression of TLR4 and the phosphorylation of NF-κB p65 were markedly inhibited by catalpol compared with the LPS group. The inflammatory damage to the mouse uterus caused by LPS was greatly reduced and was accompanied by a decline in myeloperoxidase (MPO) activity. The results of this study suggest that catalpol can exert an anti-inflammatory impact on LPS-induced bEECs and mouse endometritis by inhibiting inflammation and activation of the TLR4/NF-κB signaling pathway.

6.
Microb Pathog ; 136: 103721, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494298

RESUMO

Acute lung Injury (ALI) is the clinical syndrome of parenchymal lung disease, leading to an extremely high mortality. The pathogenesis of ALI is suggested to be a consequence of uncontrolled inflammation. Lipopolysaccharide (LPS)-induced ALI mice model is often used for the mechanism. Studies show that TGF-beta activated kinase 1 (MAP3K7) binding protein 1/2 (TAB2) plays a crucial role in LPS-induced inflammation response. Furthermore, microRNA-142a-3p (miR-142a-3p) has been observed to be involved in inflammation-induced disease. Thus, we investigated the role of miR-142a-3p and TAB2 on LPS-induced ALI, which involved the TLR4/TAB2/NF-κB signaling. ALI and normal lung tissues were collected to access the relative expression of pro-inflammatory cytokines and miR-142a-3p. Histopathological examination and Wet to Dry weight ratios of lung tissues were used to access the establishment of ALI models. Raw264.7 cells were transfected with si-TAB2 or miR-142a-3p mimics to elucidate the role of TAB2 or miR-142a-3p in the inflammatory cascade in ALI. Additionally, the relationship between miR-142a-3p and TAB2 was validated by dual-luciferase report system. Our study discovered that miR-142-3p was up-regulated both in LPS-induced ALI mice model and RAW264.7 cells model. MiR-142a-3p mimics group experienced significant decrease in the secretion of pro-inflammatory cytokines as a result of the inhibition of NF-κB signaling pathway. Bioinformatics database showed that the adaptor protein, TAB2, was critical in this pathway and it is the target gene of miR-142a-3p. Their relation was first confirmed by us via dual-luciferase report system. Results of our study demonstrated that miR-142a-3p exerts as a protective role in LPS-induced ALI through down-regulation of NF-κB signaling pathway.

7.
Mol Ther ; 27(10): 1758-1771, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31405809

RESUMO

Emerging evidence has revealed that excessive activation of macrophages may result in an adverse lung inflammation involved in sepsis-related acute lung injury (ALI). However, it has never been clearly identified whether peripheral circulating serum exosomes participate in the pathogenesis of sepsis-related ALI. Therefore, the purposes of our study were to investigate the effect of serum exosomes on macrophage activation and elucidate a novel mechanism underlying sepsis-related ALI. Here we found that exosomes were abundant in the peripheral blood from ALI mice and selectively loaded microRNAs (miRNAs), such as miR-155. In vivo experiments revealed that intravenous injection of serum exosomes harvested from ALI mice, but not control mice, increased the number of M1 macrophages in the lung, and it caused lung inflammation in naive mice. In vitro, we demonstrated that serum exosomes from ALI mice delivered miR-155 to macrophages, stimulated nuclear factor κB (NF-κB) activation, and induced the production of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6. Furthermore, we also showed that serum exosome-derived miR-155 promoted macrophage proliferation and inflammation by targeting SHIP1 and SOCS1, respectively. Collectively, our data suggest the important role of circulating exosomes secreted into peripheral blood as a key mediator of septic lung injury via exosome-shuttling miR-155.

8.
J Cell Physiol ; 234(12): 22874-22883, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31148190

RESUMO

Acute lung injury (ALI) is a severe acute inflammatory reaction of the lungs caused by a variety of factors, which can lead to a high mortality rate. MicroRNAs are a novel therapeutic molecule that play a vital role in many diseases. However, its mechanism of action in lipopolysaccharide (LPS)-induced mouse ALI is not clear. The study aimed to investigate the mechanism of action of miR-497 in LPS-induced ALI. As a result, it was found that the expression of miR-497 in the inflammatory reaction showed a decrease in time and dose trends. Importantly, miR-497 reduced LPS-induced expression levels of related inflammatory factors. In addition, we also demonstrated that IRAK2 is a direct target molecule of miR-497. Interestingly, we further found that miR-497 inhibits the expression of IRAK2 by targeting IRAK2-3'UTR. Therefore, miR-497 can partially negatively regulate the activation of IRAK2-NF-κB pathway in LPS-induced inflammatory responses.

9.
Microb Pathog ; 132: 302-312, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059756

RESUMO

Acute lung injury (ALI) is clinically characterized by excessive inflammation leading to acute respiratory distress syndrome (ARDS), having high morbidity and mortality both in human and animals. Ginsenoside Rb1 (Rb1) is a major primary bioactive component extracted by Panax ginseng, which has numerous pharmacological functions such as anti-cancer, anti-inflammatory, and antioxidant. However, the anti-inflammatory effects of Rb1 in Staphylococcus aureus (S. aureus)-induced ALI in mice have not been investigated. The aim of the current study was to determine the anti-inflammatory influence of Rb1 on S. aureus-induced ALI in mice, and to explore its possible underlying principle mechanisms in RAW 264.7 macrophage cells. The results of physical morphology, histopathological variation and wet-to-dry weight ratio of lungs revealed that Rb1 significantly attenuated S. aureus-induced lung injury. Furthermore, qPCR results displayed that Rb1 inhibited IL-1ß, IL-6 and TNF-α production both in vivo and in vitro. The activation of Toll-like receptor 2 (TLR2) by S. aureus was inhibited by application of Rb1 as confirmed by results of immunofluorescence assay. The expression of NF-kB and MAPK signaling proteins revealed that Rb1 significantly attenuated the phosphorylation of p65, ERK, as well as JNK. Altogether, the results of this experiment presented that Rb1 has ability to protect S. aureus-induced ALI in mice by attenuating TLR-2-mediated NF-kB and MAPK signaling pathways. Consequently, Rb-1 might be a potential medicine in the treatment of S. aureus-induced lung inflammation.


Assuntos
Lesão Pulmonar Aguda/microbiologia , Ginsenosídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pulmão/patologia , Masculino , Camundongos , Panax/química , Pneumonia , Células RAW 264.7/efeitos dos fármacos , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
10.
Int Immunopharmacol ; 70: 201-207, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30822611

RESUMO

Endometritis is one of the main diseases that causes great economic losses in the dairy industry. Recent studies have shown that matrine extracted from the traditional Chinese herb Sophora flavescens is an alkaloid with a broad range of bioactivities. Here, we aimed to investigate the protective effects of matrine on Staphylococcus aureus lipoteichoic acid (LTA)-induced endometritis in mice and elucidate the possible molecular mechanisms in vitro. Histopathological changes showed that matrine remarkably attenuated the uterus injury in a mouse model of LTA-induced endometritis. qPCR and ELISA results showed that matrine dose-dependently reduced the expression of pro-inflammatory cytokines (TNF-α and IL-1ß). To further elucidate the underlying mechanisms of this protective effect of matrine, LTA-stimulated bovine endometrial epithelial cells (bEECs) were employed in this study. The results demonstrated that TLR2 expression and its downstream nuclear factor (NF)-κB activation were both suppressed by matrine treatment. Furthermore, a small interference RNA targeting TLR2 gene mimicked matrine in its inhibition on LTA-induced activation of TLR2 and NF-κB. In conclusion, these findings suggest the protective effect of matrine against LTA-induced endometritis through negative regulation of TLR2-mediated NF-κB pathway.


Assuntos
Alcaloides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Endometrite/tratamento farmacológico , Medicina Tradicional Chinesa , Quinolizinas/uso terapêutico , Staphylococcus aureus/fisiologia , Útero/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Regulação para Baixo , Endometrite/induzido quimicamente , Endometrite/imunologia , Feminino , Humanos , Interleucina-1beta/metabolismo , Lipopolissacarídeos/metabolismo , Camundongos , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais , Sophora/imunologia , Ácidos Teicoicos/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Útero/patologia
11.
Theriogenology ; 130: 89-98, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30878693

RESUMO

Exosomes, one kind of extracellular vesicles, are released under abnormal and normal physiological conditions. An understanding of plasma-derived exosomal microRNA (miRNA) profiles during pregnancy will significantly contribute to knowledge of maternal-fetal communication in ruminants. In this study, we isolated plasma-derived exosomes from dairy cows during early (∼60 days, gestational day (G_D) 60), mid (∼150 days, G_D 150) and late (∼240 days, G_D 240) pregnancy. Exosomal miRNA profiles were revealed using RNA sequencing technology, and the abundance of exosomal miRNAs between each stage were compared. In the G_D150 vs. G_D60, G_D240 vs. G_D60 and G_D240 vs. G_D150stages, there were 23, 32 and 29 miRNAs, respectively, significantly differentially enriched. Significant annotations for protein binding and transport- or immunoregulatory-related categories or pathways were found for the predicted target genes of these miRNAs. In addition, we further identified specific exosomal miRNAs for each pregnancy stage, including the following: bta-miR-499, bta-miR-16a, bta-miR-20a, bta-miR-223, and bta-miR-128 in the G_D60 stage; bta-miR-493, bta-miR-127, and bta-miR-143 in the G_D150 stage; and bta-miR-122, bta-miR-182, bta-miR-183, bta-miR-200b, and bta-miR-200c in the G_D240 stage. Our findings provide new insight into maternal-fetal communication during pregnancy. Future studies will use these data to identify and characterize specific exosomal miRNA regulatory mechanisms in the maternal-fetal immune response.


Assuntos
Exossomos/metabolismo , Perfilação da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Bovinos , Feminino , Regulação da Expressão Gênica , Gravidez , Análise de Sequência de RNA/veterinária
12.
J Cell Mol Med ; 23(5): 3711-3723, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30920152

RESUMO

It is well established that cancer cells depend upon aerobic glycolysis to provide the energy they need to survive and proliferate. However, anti-glycolytic agents have yielded few positive results in human patients, in part due to dose-limiting side effects. Here, we discovered the unexpected anti-cancer efficacy of Polydatin (PD) combined with 2-deoxy-D-glucose (2-DG), which is a compound that inhibits glycolysis. We demonstrated in two breast cell lines (MCF-7 and 4T1) that combination treatment with PD and 2-DG induced cell apoptosis and inhibited cell proliferation, migration and invasion. Furthermore, we determined the mechanism of PD in synergy with 2-DG, which decreased the intracellular reactive oxygen (ROS) levels and suppressed the PI3K/AKT pathway. In addition, the combined treatment inhibited the glycolytic phenotype through reducing the expression of HK2. HK2 deletion in breast cancer cells thus improved the anti-cancer activity of 2-DG. The combination treatment also resulted in significant tumour regression in the absence of significant morphologic changes in the heart, liver or kidney in vivo. In summary, our study demonstrates that PD synergised with 2-DG to enhance its anti-cancer efficacy by inhibiting the ROS/PI3K/AKT/HIF-1α/HK2 signalling axis, providing a potential anti-cancer strategy.

13.
Int Immunopharmacol ; 70: 135-146, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30802676

RESUMO

Acute lung injury (ALI) is a common clinical syndrome of excessive uncontrolled inflammatory response in lung tissues with high mortality rates and limited therapeutic approaches. MicroRNAs (miRNAs) are a class of small non-coding RNAs which attach at 3'UTR of mRNA for further regulation of diverse proteins. MiRNAs are a current focus in regulating the inflammatory processes. The extent of pro-inflammatory gene activated against Staphylococcus aureus (S. aureus) is still unclear. Myeloid differentiation primary response 88 (MyD88) is involved in gram positive bacteria-induced lung inflammation by Toll-like receptors (TLRs). Then MyD88 activates NF-κB through IRAKs which are in charge of inflammation. Target prediction analyses revealed MyD88, a result of projections from multiple bio-websites, to be a putative target of miR-128. Here we probe the expression of the MyD88 and miRNA in mode of inflammation. We found up-regulated expression of MyD88 and down-regulation of miR-128 after S. aureus infection in mouse lung tissues and RAW264.7 cells via qPCR and western blotting (WB) analysis. Moreover, MyD88-miR-128 interaction was validated by luciferase assays. Then, we proved that miR-128 expression caused a reduction in IκBα and p65 phosphorylation and resulted in significant reduction in secretion of inflammatory cytokines, being consistent with the deletion of MyD88 in macrophages. It revealed that miR-128 specifically blocked the further development of inflammation through MyD88 down-regulation. Finally, we demonstrated a novel role of miR-128 that it mediates negative regulation in S. aureus induced inflammation by targeting MyD88.


Assuntos
Lesão Pulmonar Aguda/imunologia , Inflamação/imunologia , Pulmão/imunologia , MicroRNAs/genética , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/fisiologia , Lesão Pulmonar Aguda/genética , Animais , Regulação da Expressão Gênica , Inflamação/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Células RAW 264.7 , Transdução de Sinais , Infecções Estafilocócicas/genética
14.
Inflamm Res ; 68(3): 231-240, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30673803

RESUMO

OBJECTIVE: In both humans and animals, endometritis is severe inflammation of the uterus, and it causes great economic losses in dairy cow production. MicroRNAs have been reported to play an important role in various inflammatory diseases. However, the regulatory mechanisms of miR-19a in endometritis remain unclear. Thus, the aims of this study are to investigate the role of miR-19a in a mouse model of lipopolysaccharide (LPS)-induced endometritis and elucidate the possible mechanisms in bovine endometrial epithelial cells (bEECs). METHODS AND RESULTS: Histological analysis showed that LPS induced severe pathological changes, suggesting that the endometritis mouse model was well established. The qPCR assay indicated that miR-19a expression in the uterine tissues of mice with endometritis and in bEECs with LPS stimulation was significantly reduced. The overexpression of miR-19a significantly decreased the expression of inflammatory cytokines (TNF-α, IL-6 and IL-1ß) and the phosphorylation of NF-κB p65 and IκBα. Similar results were also obtained following the knockdown of TBK1. Furthermore, a dual luciferase reporter assay further validated that miR-19a inhibited TBK1 expression by binding directly to the 3'-UTR of TBK1. CONCLUSION: We demonstrated that miR-19a has anti-inflammatory effects and mediates the negative regulation of the NF-κB Pathway in LPS-induced endometritis by targeting TBK1.


Assuntos
Endometrite/imunologia , MicroRNAs/fisiologia , NF-kappa B/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Animais , Bovinos , Linhagem Celular , Citocinas/imunologia , Endometrite/induzido quimicamente , Endometrite/patologia , Feminino , Inativação Gênica , Humanos , Lipopolissacarídeos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Útero/imunologia , Útero/patologia
15.
Mol Med Rep ; 19(3): 2279-2286, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30664199

RESUMO

Sodium houttuyfonate (SH) has been indicated to play an important anti­inflammatory role. Previous studies have confirmed that SH can inhibit the NF­κB pathway in lipopolysaccharide (LPS)­induced mastitis in bovine mammary epithelial cells. However, the effects of SH on LPS­induced mastitis in animals should be verified to further evaluate its actual value. In the present study, the anti­inflammatory effects of SH were investigated in mouse models and a mouse mammary epithelial cell line. Hematoxylin and eosin staining (H&E) showed that SH therapy significantly alleviated the pathological changes in mammary glands. Myeloperoxidase (MPO) activity analysis demonstrated that SH substantially decreased MPO activity in vivo. RT­qPCR results showed that SH reduced the expression of interleukin (IL)­1, IL­6 and tumor necrosis factor α both in vivo and in vitro. In addition, western blot results indicated that SH suppressed the phosphorylation of nuclear factor kappa­light­chain­enhancer of activated B­cells (NF­κB) p65 protein and reduced the degradation of inhibitor of kappa light polypeptide gene enhancer in B­cells alpha protein in vivo and in vitro. These results demonstrated that SH ameliorates LPS­induced mastitis by inhibiting the NF­κB pathway.


Assuntos
Alcanos/administração & dosagem , Inflamação/tratamento farmacológico , Mastite/tratamento farmacológico , Sulfitos/administração & dosagem , Fator de Transcrição RelA/genética , Animais , Bovinos , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/patologia , Lipopolissacarídeos/toxicidade , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/patologia , Mastite/induzido quimicamente , Mastite/genética , Mastite/patologia , Camundongos , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética
16.
Reprod Sci ; 26(6): 829-838, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30526368

RESUMO

Previous studies show that methylseleninic acid (MSA), which is the most common selenium derivative used as a drug in humans, exerts specific cytotoxic effects in several cancer cell types. However, the complex mechanism of these effects has not been fully elucidated. Here, we demonstrate by Cell Counting Kit-8 in mouse breast cancer cell line 4T1 that MSA inhibits cell viability in a concentration-dependent (5, 10, 20 µmol/L) and time-dependent (6, 12, 24 hours) manner. Flow cytometry, Western blot, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analyses indicated that MSA inhibits cancer cell invasion and induces apoptosis by the activation of caspase-3, poly ADP ribose polymerase 1 (PARP1), and BCL2-associated X. Furthermore, MSA demonstrated anticancer activity by inhibiting the Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway. The MSA treatment for 24 hours decreased the phosphorylation of JAK2 and STAT3 in 4T1 cells by Western blot. We also confirmed this with the use of a JAK2 chemical inhibitor, AG490, as a positive control. In a 4T1 orthotopic allograft model, morphological and TdT-mediated dUTP nick-end labeling analyses showed that MSA treatment (1.5 mg/kg/weight) for 28 days inhibits tumor growth consistent with the clinical anticancer drug cyclophosphamide. Our observations demonstrate that MSA is a potent anticancer drug in breast cancer and uncovered a key role of the JAK2/STAT3 pathway in modulating tumor growth.

17.
Inflammation ; 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30406463

RESUMO

Endometritis is a common inflammatory disease which endangers human and animal reproductive health. MicroRNA (miRNA) let-7c plays an important role in the inflammatory process; however, the regulatory underlying mechanism of let-7c in endometritis is unclear. In this study, we confirmed that let-7c was significantly reduced in LPS-induced mouse endometritis model, and overexpression of let-7c was able to effectively reduce uterine tissue damage caused by lipopolysaccharide (LPS), and then, a LPS-induced bovine endometrial epithelial cell (BEND) line was used to mimic the inflammatory model in vitro. Our data showed that overexpression of let-7c significantly reduced the expression of pro-inflammatory cytokines in BEND cells induced by LPS. Meanwhile, immunofluorescence and western blotting results showed that let-7c significantly inhibited LPS-induced phosphorylation of NF-κB, thereby inhibiting downstream pro-inflammatory cytokine expression. Taken together, our results suggested that let-7c ameliorates LPS-induced endometritis by attenuating the expression of pro-inflammatory cytokines via inhibition of the activation of NF-κB.

18.
Biochem Biophys Res Commun ; 505(1): 1-6, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30224056

RESUMO

Previous studies have shown that shikonin(SHI), the bioactive naphthoquinone constituent extracted from Chinese herb Lithospermum Erythrorhizon, possesses the potential to confront inflammation, and has little concerns towards drug residues comparing with antibiotics. While mastitis in dairy industry always trigger great harm to milk yields, effects of SHI on lipopolysaccharides (LPS)-induced mastitis should be measured. Here, we demonstrate anti-inflammatory effects of SHI on LPS-challenged mastitis and elucidate the potential signaling pathway both in vivo and in vitro. As a result, SHI administration mice significantly suffered less impairment of mammary gland and less recruitment of neutrophils than LPS administration mice. SHI significantly suppressed the expression of p-IκBα and p-p65, which are the critical proteins functioning in NF-kB signaling pathway. qPCR results indicate decreasing level of upstream pro-inflammatory cytokines in tissues, such as TNF-α, IL-1ß, and IL-6. The results are corresponding with the results in vitro, suggesting the potential usage of SHI as a therapeutic medicine in mastitis.

19.
Front Immunol ; 9: 1916, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30186287

RESUMO

Bovine endometritis affects milk production and reproductive performance in dairy cows and causes serious economic loss. The underlying molecular mechanisms or signaling pathways of bovine endometritis remain unclear. In this study, we attempted to determine the expression mechanism of mir-223 in endometritis of dairy cows and evaluate its potential therapeutic value. We first confirmed that there was an increased level of miR-223 in endometritis, and then, an LPS-induced bovine endometrial epithelial cell (BEND) line was used to mimic the inflammatory model in vitro. Our data showed that activation of NF-κB promoted the transcription of miR-223, thus inhibiting activation of the inflammatory mediator NLRP3 and its mediation of IL-1ß production to protect against inflammatory damage. Meanwhile, in vivo studies showed that inhibition of mir-223 resulted in an enhanced pathology of mice during LPS-induced endometritis, while overexpression of mir-223 attenuated the inflammatory conditions in the uterus. In summary, our study highlights that miR-223 serves both to constrain the level of NLRP3 activation and to act as a protective factor in the inflammatory response and thus provides a future novel therapeutic modality for active flares in cow endometritis and other inflammatory diseases.

20.
Front Pharmacol ; 9: 982, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214410

RESUMO

Acute lung injury (ALI) which is featured by a strong pulmonary inflammation, is a major cause of morbidity and mortality in critically ill patients. Magnoflorine, a quaternary alkaloid isolated from Chinese herb Magnolia or Aristolochia, has been reported to have potent anti-inflammatory properties. However, the effect of magnoflorine on lipopolysaccharide (LPS)-induced ALI in mice has not been reported. The purpose of the present study is to investigate the anti-inflammatory effect of magnoflorine on LPS-induced ALI and elucidate its possible molecular mechanisms in RAW264.7 cells. The results of histopathological changes as well as the myeloperoxidase (MPO) activity indicated that magnoflorine significantly alleviated the lung injury induced by LPS. In addition, qPCR results showed that magnoflorine dose-dependently decreased the expression of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6. Immunofluorescence assay also confirmed that the level of Toll-like receptor 4 (TLR4) induced by LPS was inhibited by magnoflorine treatment. Further experiments were performed using Western blotting to detect the expression of related proteins in the NF-κB and MAPK signaling pathways. The results showed that magnoflorine suppressed the levels of phosphorylated p65, IκBα, p38, ERK, and JNK. In conclusion, all data indicate that magnoflorine could protect against LPS-induced inflammation in ALI at least partially by inhibiting TLR4-mediated NF-κB and MAPK signaling pathways.

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