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1.
Cytokine ; 175: 156498, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38176086

RESUMO

S. aureus isolated from bacterial bovine endometritis is common in epidemiological reports, but is often ignored as a subclinical pathogenic microorganism. In a previous study, we showed that live S. aureus (LSA) and heat killed S. aureus (HK-SA) induce different inflammatory responses in bovine endometrial tissue, and possibly being associated with the accumulation of prostaglandin E2 (PGE2). Thus, in this study, we varied PGE2 concentrations using inhibitors or agonists in HK-SA-treated bovine endometrial tissues. The results demonstrated that PGE2 has a positive relationship with IL-6, TNF-α, and damage-associated molecular patterns (DAMPs; e.g., HMGB-1 and HABP-1) expression and tissues damage, and is regulated by the EP4-p38 MAPK pathway. We concluded that lipoproteins of S. aureus are associated with PGE2 generation. To further explore the relationship between LSA and PGE2 accumulation, we used the S. aureus strain SA113 lipoprotein knockout (SA113Δlpl) to infect bovine endometrial epithelial cells (BECs). LSA decreased PGE2, cAMP, EP4, IL-6, IL-8, cAMP secretion, and the MAPK and PKA signaling pathways when infected with SA113Δlpl, as compared with SA113-infected groups. Moreover, the adhesion and invasion of BECs were similarly downregulated when lipoproteins in S. aureus were knocked out. The results of this study show that PGE2 is involved in both HK-SA- and LSA-induced inflammatory responses in the bovine endometrium. We suggest that S. aureus infection is associated with bovine endometritis, and although HK-SA and LSA induce different inflammatory responses, the strategy of decreasing PGE2 accumulation is helpful in reducing the inflammation stage caused by S. aureus.


Assuntos
Endometrite , Staphylococcus aureus Resistente à Meticilina , Feminino , Humanos , Animais , Bovinos , Dinoprostona/metabolismo , Staphylococcus aureus Resistente à Meticilina/metabolismo , Staphylococcus aureus/metabolismo , Interleucina-6 , Lipoproteínas , Receptores de Prostaglandina E Subtipo EP4/metabolismo
2.
Reproduction ; 160(6): 853-862, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33112787

RESUMO

Although urokinase-type plasminogen activator (PLAU) and urokinase-type plasminogen activator receptor (PLAUR) have been reported to play key roles in ovarian function, their precise contribution to mammalian follicular development remains unclear. In this study, we first observed that PLAU and PLAUR were present in bovine granulosa cells (GCs). Following culture of granulosa cells with PLAU (0.5 ng/mL) and PLAUR antibody (10 µg/mL) separately and together for 24 or 48 h, a proliferation assay showed that interaction between PLAU and PLAUR contributes to bovine GC proliferation. To study the potential pathways involved in PLAU/PLAUR-induced cell proliferation, ELISA and Western blotting were performed. We found that PLAU significantly increased the ratio of phosphorylated to non-phosphorylated ERK1/2 through PLAUR signaling. Further treatment with U0126, a specific ERK1/2 phosphorylation inhibitor, markedly suppressed PLAU/PLAUR-induced ERK1/2 phosphorylation and cell proliferation. In addition, we found that PLAU and PLAUR significantly increased the intracellular cAMP level and the use of Rp-cAMP, a specific PKA inhibitor, prevented PLAU/PLAUR from promoting activation of the ERK1/2 pathway and GC proliferation. Therefore, the interaction between PLAU and PLAUR may be involved in accumulating cAMP signals and enabling MAPK/ERK1/2 activation, affecting GC proliferation. Here, we provide new mechanistic insights into the roles of PLAU and PLAUR on promoting bovine GC proliferation. The finding that potential cross-points between PLAU/PLAUR-induced intracellular signals affect GC proliferation will help in understanding the mechanisms regulating early follicular development.


Assuntos
Proliferação de Células , AMP Cíclico/metabolismo , Células da Granulosa/citologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Animais , Bovinos , Feminino , Células da Granulosa/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Fosforilação , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genética , Transdução de Sinais , Ativador de Plasminogênio Tipo Uroquinase/genética
3.
Front Microbiol ; 14: 1163261, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168122

RESUMO

Introduction: In clinical settings, dairy cows are often attacked by pathogenic bacteria after delivery, especially Staphylococcus aureus (S. aureus). Neutrophils have long been regarded as essential for host defense against S. aureus. Prostaglandin E2 (PGE2) can additionally be used as an inflammatory mediator in pathological conditions to promote the repair of inflammatory injuries. However, whether S. aureus can promote the accumulation of PGE2 after the infection of neutrophils in cows and its mechanism remain unclear. Lipoprotein is an important immune bioactive ingredient of S. aureus. Methods: In this study, the changes in neutrophils were monitored in dairy cows infected with wild-type S. aureus (SA113) and an S. aureus lipoprotein-deficient strain (Δlgt); meanwhile, we established whether pattern recognition receptors mediate this process and whether S. aureus lipoproteins are necessary for causing the release of PGE2 from cow neutrophils. Results: The results showed that Δlgt was less effective than SA113 in inducing the production of IL-1ß, IL-6, IL-8, IL-10, and PGE2 within neutrophils; furthermore, TLR2, TLR4, and NLRP3 receptors were found to mediate the inducible effect of lipoprotein on the above inflammation mediators and cytokines, which depended on MAPK and Caspase-1 signaling pathways. In addition, TLR2, TLR4, and NLRP3 inhibitors significantly inhibited PGE2 and cytokine secretion, and PGE2 was involved in the interaction of S. aureus and neutrophils in dairy cows, which could be regulated by TLR2, TLR4, and NLRP3 receptors. We also found that S. aureus was more likely to be killed by neutrophils when it lacked lipoprotein and TLR2, TLR4, and NLRP3 were involved, but PGE2 seemed to have no effect. Discussion: Taken together, these results suggest that lipoprotein is a crucial component of S. aureus in inducing cytokine secretion by neutrophils as well as killing within neutrophils, which could be accomplished by the accumulation of PGE2 by activating MAPK and the Caspase-1 signaling pathways through TLR2, TLR4, and NLRP3 receptors. These results will contribute to a better understanding of the interaction between S. aureus and host immune cells in dairy cows.

4.
Ann Palliat Med ; 10(7): 7794-7801, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353066

RESUMO

BACKGROUND: The treatment of choledocholithiasis by endoscopic retrograde cholangiopancreatography (ERCP) is a difficult endoscopic procedure involving a complicated surgical process. During and after ERCP, surgery-related complications may occur, and serious complications can threaten the life of the patient. This study aims to evaluate the correlation between the possible complications of ERCP treatment of choledocholithiasis and the quality of life of patients, and to provide a basis for formulating corresponding intervention measures. METHODS: Using the Gastrointestinal Quality of Life Index (GIQLI) and the MOS item short from health survey (SF-36), we conducted random telephone follow-ups of 194 patients admitted to The Second Affiliated Hospital of Soochow University who underwent ERCP for the treatment of choledocholithiasis from October 2017 to December 2020. The patients' complications symptoms and quality of life were recorded, and a comparative analysis was performed. RESULTS: During the hospitalization of the included 194 patients, complications occurred in 38 cases (19.6%), including 18 cases (9.3%) of hyperamylase, 11 cases (5.7%) of acute pancreatitis, and 5 cases (2.6%) of cholecystitis. There were 4 cases (2.1%) of gastrointestinal bleeding. The SF-36 scores in the complication group were significantly lower than those in the non-complication group across various dimensions, including bodily pain (BP), general health (GH), vitality (VT), social functioning (SE), and mental health (MH). Furthermore, the GIQLI scores in the complication group were lower than those in the non-complication group across various dimensions, including symptoms, subjective symptoms, physical function status, social activity status, as well as mental and psychological status. Multiple regression analysis showed that dimensions such as PF, BP, and subjective symptoms were more likely to be affected by hyperamylaseemia, acute pancreatitis, and cholecystitis, and the difference was statistically significant (P<0.05). CONCLUSIONS: Complications after ERCP result in a poor quality of life after discharge in choledocholithiasis patients, suggesting that nurses need to take effective measures to prevent and actively treat hyperamylase, acute pancreatitis, and acute pancreatitis during the hospitalization of holedocholithiasis patients after ERCP. Common complications, such as cholecystitis, promote the recovery of patients and reduce the impact of the disease on quality of life.


Assuntos
Coledocolitíase , Pancreatite , Doença Aguda , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Coledocolitíase/cirurgia , Humanos , Pancreatite/etiologia , Alta do Paciente , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Estudos Retrospectivos
5.
Artigo em Inglês | MEDLINE | ID: mdl-29482767

RESUMO

Postpartum bacterial infections of the uterus cause endometritis in dairy cows. Inflammatory responses to bacterial infections in the bovine uterus were generated through pattern recognition receptors (PRRs) that bind to pathogen-associated molecules such as lipopolysaccharide (LPS) from Escherichia coli. Among these PRRs, Toll-like receptor 4 (TLR4) is primarily responsible for LPS recognition, which triggers inflammatory responses via mitogen-activated protein kinases (MAPKs) and NF-κB signaling activation, resulting in the expression of inflammatory mediators in mammals such as IL-8 and IL-6. Previous studies indicate that PGE2 plays an important role in bacterial endometritis, although details on the mechanism underlying how it regulates LPS-induced inflammatory responses in bovine endometrial epithelial cells (bEECs) remain elusive. In the present study, bEECs were pre-treated with exogenous PGE2 and/or PGF2α prior to LPS stimulation. With PGE2 pre-treatment, we observed an augmentation in LPS-stimulated PKA, ERK, and IκBα phosphorylation and cyclooxygenase-2 (COX-2) and anti-inflammatory cytokine IL-6 expression and downregulation of prostaglandin E2 receptor 4 (EP4) and TLR4 in bEECs. These results indicate that LPS-induced inflammatory responses through TLR4 signaling in bEECs could be downregulated by exogenous PGE2 pre-treatment, but not PGF2α.


Assuntos
Dinoprostona/farmacologia , Células Epiteliais/efeitos dos fármacos , Lipopolissacarídeos/antagonistas & inibidores , NF-kappa B/genética , Receptor 4 Toll-Like/genética , Animais , Bovinos , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas Quinases Dependentes de AMP Cíclico/imunologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Endométrio/citologia , Endométrio/efeitos dos fármacos , Endométrio/imunologia , Células Epiteliais/citologia , Células Epiteliais/imunologia , Feminino , Regulação da Expressão Gênica , Inflamação , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Lipopolissacarídeos/farmacologia , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/imunologia , Modelos Biológicos , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/imunologia , NF-kappa B/imunologia , Cultura Primária de Células , Transdução de Sinais , Receptor 4 Toll-Like/imunologia
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