首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献，搜索用时 93 毫秒
1.
β‐carotene is one of the most abundant carotenoids, has potential anti‐inflammatory effect, it has been reported that β‐carotene could suppress LPS‐induced inflammatory responses by inhibiting nuclear factor kappa B (NF‐κB) translocation, but the more detailed molecular mechanisms underlying the anti‐inflammatory action of β‐carotene remain to be fully understood. In this study, we investigated the influence of β‐carotene on the activation of JAK2/STAT3, MAPK, and NF‐κB signaling pathway induced by LPS in RAW264.7 cells and peritoneal macrophages. Cells were treated with different concentrations of β‐carotene for 3 hr after LPS treatment for 24 hr. The mRNA expression and the release of IL‐1β, IL‐6, and TNF‐α were evaluated by RT‐PCR and ELISA, and the level of signaling proteins of JAK2/STAT3, MAPK, and NF‐κB signaling pathway were detected by Western blot. The results showed that β‐carotene significantly suppressed (p < 0.05) LPS‐induced release of IL‐1β, IL‐6, and TNF‐α and their mRNA expression. LPS‐induced JAK2/STAT3, IκB/NF‐κB p65, JNK/p38 MAPK signal activation were significantly attenuated (p < 0.05) by β‐carotene in a dose‐dependent manner. In conclusion, β‐carotene could attenuate LPS‐induced inflammation via inhibition of the NF‐κB, JAK2/STAT3, and JNK/p38 MAPK signaling pathways in macrophages.  相似文献   

2.
  相似文献   

3.
  相似文献   

4.
Au, A. Y., Hasenwinkel, J. M., Frondoza, C. G. Silybin inhibits interleukin‐1β‐induced production of pro‐inflammatory mediators in canine hepatocyte cultures. J. vet. Pharmacol. Therap. 34 , 120–129. Hepatocytes are highly susceptible to cytokine stimulation and are fundamental to liver function. We established primary canine hepatocyte cultures to study effects of anti‐inflammatory agents with hepatoprotective properties. Hepatocyte cultures were incubated with control media alone, silybin (SB), or the more bioavailable silybin–phosphatidylcholine complex (SPC), followed by activation with interleukin‐1 beta (IL‐1β; 10 ng/mL). Inflammatory response was measured by prostaglandin E2 (PGE2), interleukin‐8 (IL‐8), and monocyte chemotactic protein‐1 (MCP‐1) production and also nuclear factor‐kappa B (NF‐κB) translocation. Hepatocyte cultures continued production of the phenotypic marker albumin for more than 7 days in culture. IL‐1β exposure increased PGE2, IL‐8, and MCP‐1 production, which was paralleled by NF‐κB translocation from the cytoplasm to the nucleus. Pretreatment with SB and SPC significantly inhibited IL‐1β‐induced production of pro‐inflammatory markers and attenuated NF‐κB nuclear translocation. We demonstrate for the first time that primary canine hepatocyte cultures can be maintained in culture without phenotypic loss. The observation that hepatocyte cultures respond to pro‐inflammatory IL‐1β activation indicates hepatocytes as primary cellular targets of extrinsic IL‐1β. The ability of SB and SPC to inhibit hepatocyte culture activation by IL‐1β reinforces the notion of their hepatoprotective effects. Our primary canine hepatocyte culture model facilitates identification of hepatoprotective agents and their mechanism of action.  相似文献   

5.
Reactive oxygen species (ROS) have been shown to have a role in inflammation. We investigated whether Forsythia suspensa extract (FSE) could exert its antioxidant potential against lipopolysaccharide (LPS)‐induced inflammatory liver injury in rats. Rats were orally fed FSE once daily for 7 consecutive days prior to LPS (Escherichia coli, serotype O55:B5) injection. LPS treatment caused liver dysfunction as evidenced by massive histopathological changes and increased serum alanine aminotransferase and aspartate aminotransferase activities which were ameliorated by FSE pretreatment. FSE attenuated LPS‐induced depletion of cytosolic nuclear factor‐erythroid 2‐related factor 2 (Nrf2) and suppression of Nrf2 nuclear translocation in liver, and the generation of ROS and malondialdehyde in serum and liver. FSE increased the Nrf2‐mediated induction of heme oxygenase‐1 in liver, as well as superoxide dismutase and glutathione peroxidase activities in serum and liver. Importantly, FSE attenuated LPS‐induced nuclear factor‐кB (NF‐кB) nuclear translocation in liver, and subsequently decreased tumor necrosis factor‐α, interleukin (IL)‐1β and IL‐6 levels in serum and liver, which were associated with FSE‐induced activation of Nrf2 in liver. These results indicate that the protective mechanisms of FSE may be involved in the attenuation of oxidative stress and the inhibition of the NF‐кB‐mediated inflammatory response by modulating the Nrf2‐mediated antioxidant response against LPS‐induced inflammatory liver injury.  相似文献   

6.
  相似文献   

7.
As Kupffer cells are highly involved in the regulation of hepatic inflammatory response, the main goal of this study was to improve and to characterize a hepatocyte–Kupffer cell co‐culture of pig origin for modelling endotoxin‐induced hepatic inflammation and for testing the efficacy of potential anti‐inflammatory substances. This monolayer co‐culture was prepared from primary isolated swine hepatocytes and Kupffer cells in the ratio of 6:1 and 2:1, mimicking different states of liver inflammation. The prepared cell cultures were characterized by immunohistochemical CD‐68 detection. Lipopolysaccharide (LPS) challenge of both co‐cultures resulted in elevated interleukin‐8 (IL‐8) and that of 6:1 co‐cultures in increased IL‐6 production with a higher extent than on hepatocyte monocultures, justifying the key role of Kupffer cells in pro‐inflammatory cytokine production. LPS‐induced IL‐8 production was successfully attenuated by concomitant application of both sodium butyrate and terpinen‐4‐ol on hepatocyte monocultures, but not on co‐cultures, demonstrating the importance of the presence of Kupffer cells in cell cultures as inflammatory models. Based on these initial data, the applied porcine primary hepatocyte–Kupffer cell co‐culture is suggested to be a proper tool for in vitro investigations on liver physiology and hepatic inflammation in pigs and can be used as a useful model mimicking in vivo conditions in veterinary research.  相似文献   

8.
This study evaluated the effects of berberine on growth performance, immunity, haematological parameters, antioxidant capacity, and the expression of immune response‐related genes in lipopolysaccharide (LPS)‐challenged broilers. We assigned 120 one‐day‐old male broilers (Ross 308) to two treatment groups; each group included two subgroups, each of which included six replicates of five birds per replicate. The experiment used a 2 × 2 factorial arrangement with berberine treatment (0 or 60 mg/kg dietary) and challenge status [injection of saline (9 g/L w/v) or LPS (1.5 mg/kg body weight)] as the main factors. On days 14, 16, 18 and 20, broilers were intraperitoneally injected with LPS or physiological saline. Blood and liver samples were collected on day 21. Dietary berberine supplementation significantly alleviated the compromised average daily gain and average daily feed intake (p < 0.05) caused by LPS. The LPS challenge led to increased lymphocyte and white blood cell (WBC) counts, malondialdehyde (serum and liver) content, and immunoglobulin G and M, tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) expression (p < 0.05) and significantly reduced serum total superoxide dismutase (T‐SOD) activity (p < 0.05). Dietary berberine significantly mitigated the LPS‐induced decreases in the mRNA expression of nuclear factor‐kappa B (NF‐κB), TNF‐α, IL‐1β, inducible nitrite synthase and cyclooxygenase‐2 (p < 0.05) in the liver. In conclusion, berberine supplementation has a positive effect on LPS challenge, which may be related to the increase in antioxidant enzyme activity and inhibition of both NF‐κB signalling and the expression of inflammatory mediators.  相似文献   

9.
Weaning is characterized by intestinal inflammation, which is a big challenge in pig industry. Control of intestinal inflammation is important for improvement of growth performance and health. Therefore, the study was focused on the anti‐inflammatory activity of low‐molecular‐weight chitosan oligosaccharide (LCOS) in a porcine small intestinal epithelial cell line (IPEC‐J2). The results showed that TNF‐α, as inflammation inducer, significantly upregulated the mRNA expression of IL‐8 and MCP‐1. Afterwards, LCOS significantly attenuated mRNA expression of IL‐8 and MCP‐1 induced by TNF‐α in the cells. Mannose (MAN), as ligand of mannose receptor, had no effect on the anti‐inflammatory activity of LCOS, which suggested that mannose receptor may not involve in the anti‐inflammatory activity of LCOS in IPEC‐J2 cells. Interestingly, N‐[2‐(p‐bromocinnamylamino)ethyl]‐5‐isoquinolinesulfonamide 2HCl hydrate (H89), as PKA (protein kinase A)‐specific inhibitor, reversed the mRNA expression of IL‐8 when co‐cultured with LCOS. Furthermore, LCOS concentration dependent downregulated the mRNA expression of claudin‐1 compared with TNF‐α treatment. However, the trans‐epithelial electric resistance (TEER) was not affected by LCOS when co‐cultured with TNF‐α in 3 hr. In conclusion, LCOS have a potent anti‐inflammatory activity, and as a feed additives, may be useful for the inhibition of inflammatory process in weaning period of pigs with intestinal inflammation occurring.  相似文献   

10.
This study aimed to investigate the effects of back‐fat thickness (BF), at mating of sows, on placental lipotoxicity, oxidative stress, and inflammation. We performed iTRAQ labeling‐based proteomic analysis on term placentas obtained by vaginal delivery from BFI (15–20 mm, control) and BFII (21–27 mm, obese) sows formed according to BF at mating. Proteomic analysis revealed 413 proteins to be significantly different in placenta from BFII sows by ≥1.2‐fold. Gene ontology (GO) analysis identified proteins related to lipid metabolism and inflammatory response to be altered in placenta from obese sows. Indicative of a lipotoxic placental environment, increased placental lipid, and up‐regulated mRNA expression of lipogenic genes, including ADRP (p = .06), PPARD, FASN, ACACA, DGAT1, and LIPIN3, were associated with decreased AMPK and increased activation of WNT signaling in placenta from BFII group (p < .05). Furthermore, we observed a 18% decrease in total antioxidant capacity (TAC), increased mRNA content of pro‐inflammatory cytokines IL‐6, IL‐18, and TNF‐α, and increased activation of inflammatory NF‐κB and JNK signaling in placenta from BFII sows that was significantly associated with macrophage accumulation (p < .05). These findings suggest that maternal obesity aggravates a lipotoxic environment in pig term placenta that may be associated with placental dysfunction and impaired fetal growth.  相似文献   

11.
Reasons for performing study: Further knowledge of equine keratinocyte physiology and keratinocyte response to various stimuli is important in developing a better understanding of disease states involving the epidermis. Objectives: To assess the inflammatory cytokine response of cultured equine keratinocytes to various pathogen‐associated molecular pattern molecules (PAMPs) from both Gram‐negative and positive bacteria likely to be present in equine sepsis. Methods: Keratinocytes were isolated from skin of 2 horses and primary cultures performed. Keratinocytes were harvested for RNA extraction after exposure to lipopolysaccharide (LPS), lipoteichoic acid (LTA), peptidoglycan (PGN), bacterial DNA (CpG), flagellin or maintained in medium (controls) for 4 or 24 h. Real time‐quantitative PCR was used to quantify interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and CXCL8 mRNA concentrations. Results: Increases (P<0.05) in IL‐1β, IL‐6 and CXCL8 mRNA concentrations were induced by LPS exposure compared to controls. Increased mRNA concentrations of both IL‐6 and CXCL8 were also noted (vs. controls) upon exposure to flagellin. Overall, responses were greater at 4 h. No increases (P>0.05) in cytokine expression by keratinocytes were present after LTA, PGN or CpG exposure. Conclusions: Increased proinflammatory cytokine expression in response to LPS and flagellin indicate that equine keratinocytes have functional TLR4 and TLR5 receptor signalling. However, the lack of keratinocyte stimulation by PGN, LTA or CpG provides no evidence for functional TLR2, TLR9 or NOD receptor signalling. These results suggest that equine keratinocytes are more responsive to PAMPs usually associated with Gram‐negative sepsis and unresponsive to PAMPs most commonly associated with Gram‐positive sepsis. Potential relevance: The increased incidence of injury of epidermal structures in clinical cases of Gram‐negative (vs. Gram‐positive) sepsis in the horse may be due to a lack of functional TLR signalling for Gram‐positive PAMPs in the equine keratinocyte.  相似文献   

12.
Since William Coley utilized bacterial immunotherapy to treat sarcomas in the late 19th century, an association between infection and improved survival has been reported for human and canine osteosarcoma patients. One of the reasons for this improved survival is likely a reactivation of the host immune system towards an inflammatory anti‐tumour response, and one of the key players is the macrophage. Yet, despite their importance, the response of macrophages to infectious agents in the context of osteosarcoma has not been thoroughly evaluated. The aim of this study was to evaluate how in vitro exposure to a bacterial agent (Staphylococcus aureus) influenced canine and human macrophage differentiation in the presence of osteosarcoma. Our hypothesis was that S. aureus would, in the presence of osteosarcoma, induce a macrophage phenotype with significantly increased inflammatory signatures. Consistent with our hypothesis, human macrophages co‐cultured with osteosarcoma and S. aureus exhibited increased IFN‐γ, TNF‐α and IL‐12p70 cytokine secretion, decreased TGF‐β cytokine secretion and increased mRNA expression of TNF‐α when compared with macrophages co‐cultured with osteosarcoma and to macrophages cultured alone. Canine macrophages similarly exhibited increased IFN‐γ and TNF‐α cytokine secretion, decreased TGF‐β cytokine secretion, increased mRNA expression of TNF‐α and increased surface receptor expression of CD80 when co‐cultured with osteosarcoma and S. aureus. Collectively, the findings of this study suggest that infection upregulates the inflammatory immune response to counteract osteosarcoma‐induced immune suppression. This work informs a potential therapeutic strategy to optimize inflammatory stimuli for triggering an anti‐osteosarcoma macrophage response.  相似文献   

13.
为了探究硒是否影响二十二碳六烯酸(DHA)在脂多糖(LPS)诱导巨噬细胞炎性反应中发挥的抗炎作用。小鼠巨噬细胞系RAW264.7细胞分别经10μg/m L DHA、10μg/m L DHA+0.05μmol/L亚硒酸钠、1μg/m L LPS、10μg/m L DHA+1μg/m L LPS、10μg/m L DHA+1μg/m L LPS+0.05μmol/L亚硒酸钠诱导24 h,同时设置无添加的正常组。采用半定量反转录PCR检测细胞肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)和白细胞介素10(IL-10)mRNA表达量,酶联免疫吸附测定(ELISA)法测定培养液上清液中TNF-α、IL-1β、IL-6和IL-10含量。结果显示,添加亚硒酸钠(0.05μmol/L)不仅显著或极显著增强了DHA(10μg/m L)对LPS(1μg/m L)诱导RAW 264.7细胞中促炎细胞因子TNF-αmRNA表达(P0.05)和IL-1β生成(P0.01)的抑制作用,还极显著增强了DHA(10μg/m L)对LPS(1μg/m L)诱导RAW264.7细胞中抗炎细胞因子IL-10 mRNA表达的促进作用(P0.01)。由此提示,硒可增强DHA在LPS诱导巨噬细胞炎症反应中的抗炎作用。  相似文献   

14.
Objective – To determine whether older dogs will have a more pronounced pro‐inflammatory response and blunted anti‐inflammatory response to pathogen‐associated molecular patterns (PAMPs) compared with younger dogs. Design – Prospective. Setting – University teaching hospital. Animals – Thirty‐eight privately owned sexually altered dogs of various ages. Interventions – Blood was collected for HCT, WBC count, plasma biochemical analysis, and whole blood culture. Whole blood was stimulated with lipopolysaccharide (LPS) or, lipoteichoic acid or, peptidoglycan or, addition of phosphate‐buffered saline. Tumor necrosis factor (TNF), interleukin (IL)‐6, and IL‐10 production from whole blood were compared among young, middle aged, and geriatric dogs. Measurements and Main Results – LPS, lipoteichoic acid, and peptidoglycan stimulated significant TNF, IL‐6, and IL‐10 production from canine whole blood compared with phosphate‐buffered saline. Whole blood from geriatric dogs had a blunted IL‐10 response to LPS stimulation and middle‐aged dogs had increased LPS‐induced TNF production compared with the other groups. Conclusion – PAMPs from gram‐positive and gram‐negative bacteria stimulate TNF, IL‐6, and IL‐10 production from canine whole blood. The inflammatory mediator response to PAMPs from gram‐negative bacteria alters with age and may be one factor contributing to mortality in geriatric dogs with sepsis.  相似文献   

15.
To investigate the role of polysaccharide from Acanthopanax senticosus (ASPS) on lipopolysaccharide (LPS)‐induced intestinal injury, mice in three treatments were administrated orally with or without ASPS (300 mg/kg body weight) for 14 days, followed by challenge with LPS or saline. At 4 h post‐injection, blood and intestinal samples of six mice / treatment were collected. The results showed ASPS ameliorated LPS‐induced intestinal morphological deterioration, proven by improved villus height (P < 0.05) and villus height : crypt depth ratio (P < 0.05). ASPS also elevated the mucosal barrier of LPS‐challenged mice, supported by reduced plasma diamine oxidase (DAO) activity (P < 0.05) and L‐lactate (P < 0.05), increased mucosal DAO activity (P < 0.05) as well as enhanced intestinal tight junction proteins expression involving occludin‐1 (P < 0.05) and zonula occludens‐1 (P < 0.05). In addition, ASPS decreased LPS‐induced secretion of inflammatory mediators, including tumor necrosis factor (TNF)‐α (P < 0.05) and prostaglandin E2 (P < 0.05). Also, ASPS down‐regulated messenger RNA expression of toll‐like receptor 4 (TLR4) and its downstream signals, including myeloid differentiation factor 88 (P < 0.05), TNF‐α receptor‐associated factor 6 (P < 0.05), as well as nuclear factor (NF)‐κB p65 (P < 0.05) and its protein expression. These findings suggest that ASPS improves intestinal integrity under inflammation conditions connected with inhibiting TLR4/NF‐κB signaling pathways.  相似文献   

16.
  相似文献   

17.
IgE‐mediated late‐phase reactions can be induced in the skin of normal and atopic dogs by intradermal injections of anti‐IgE antibody. The histology of these reactions is very similar to that of naturally occurring atopic dermatitis. To characterize the cellular, cytokine and chemokine responses in the skin of placebo‐ and prednisolone‐treated dogs, normal beagles received either placebo or 0.5 mg/kg prednisolone twice daily for three days prior to intradermal injection of polyclonal rabbit anti‐canine IgE. Eight‐millimetre punch biopsy skin samples were taken before injection and at the injection sites after 6, 24 and 48 h. Histological and immunohistochemical examination revealed a rapid cellular influx. Eosinophil and neutrophil numbers increased from <1 to 61.4 ± 14.1, and from 7 to 62.2 ± 10.8 cells/mm2, respectively, within 6 h after injection, and remained moderately elevated 48 h later. The numbers of CD1c+, CD3+ and CD4+ mononuclear cells were also increased by 6 h. Taqman analysis demonstrated 2.5‐ to 72‐fold increases in mRNA expression for IL‐13, IL‐5, MCP (CCL2), RANTES (CCL5) and TARC (CCL17). Levels of mRNA for IL‐2, IL‐4, IL‐6, and IFNγ remained negligible. Prednisolone administration suppressed the influx of neutrophils and eosinophils, and the expression of IL‐13, CCL2, CCL5 and CCL17 (33, 97, 58, 86, 73 and 90%, respectively), as well as the influx of CD1c+ and CD3+ cells. These data document the cytokine and chemokine response to anti‐IgE injection and demonstrate the anti‐inflammatory effect of prednisolone. Funding: Schering‐Plough Animal Health.  相似文献   

18.
Effect of dietary supplementation of astaxanthin (Ax) from Phaffia rhodozyma on lipopolysaccharide‐induced inflammatory responses was investigated in male broiler chickens fed a corn‐based diet. Birds (1 week of age) were fed a corn‐enriched diet containing either 0 or 100 ppm Ax for 2 weeks and were intraperitoneally injected with lipopolysaccharide (LPS, 1 mg/kg body weight). Inflammatory responses were evaluated by determining changes in expression of messenger RNA (mRNA) in cytokines and mediators related to inflammatory responses (interleukin (IL)‐1 beta and ‐6, inducible nitrite synthase (iNOS), interferon (IFN)‐ γ and cyclooxygenase (Cox)‐2 in the liver and spleen after 2 h of LPS injection and plasma ceruloplasmin concentration as an acute phase protein. Birds fed Ax showed significantly higher iNOS mRNA expression in the liver and spleen compared to that of control birds. Ax‐fed birds also showed greater increase in mRNA expression in the liver of IL‐1, IL‐6 and IFN‐γ compared to that of control birds. The enhancing effect of Ax was further progressed when LPS was injected. No difference was found in plasma ceruloplasmin concentration between the Ax‐fed group and control group. The results suggest that feeding supplementation of Ax (100 ppm) to a corn‐enriched diet possibly does not have anti‐inflammatory effect in male broiler chickens.  相似文献   

19.
Improving our understanding of the mechanisms controlling the corpus luteum (CL) and its role in regulating the reproductive cycle should lead to improvements in the sustainability of today's global animal industry. The corpus luteum (CL) is a transient endocrine organ composed of a heterogeneous mixture steroidogenic, endothelial and immune cells, and it is becoming clear that immune mechanisms play a key role in CL regulation especially in luteolysis. Toll‐like receptors (TLR) mediate innate immune mechanisms via the production of pro‐inflammatory cytokines, especially within various tissues, although the role of TLR within CL remains unknown. Thus, the objectives of this study were to characterize TLR mRNA expression in the CL during the oestrous cycle and in pregnancy (day 30–50), and to examine the role of TLR signalling in luteal cells. Corpora lutea were collected at various stages of the cycle and pregnancy and analysed for TLR and cytokine mRNA expression. In addition, luteal cells were cultured with the TLR4 ligand (lipopolysaccharide, LPS) for 24 h to evaluate the role of TLR4 in regulating luteal function. Toll‐like receptors 1, 2, 4, 6, tumour necrosis factor alpha (TNF), interferon gamma (IFN‐G), and interleukin (IL)‐12, mRNA expressions were greatest in regressing CL compared with earlier stages (p < .05), whereas no change was observed for IL‐6 mRNA expression. Cytokine mRNA expression in cultured luteal cells was not altered by LPS. Based on these data, one or more of the TLRs found within the CL may play a role in luteolysis, perhaps via pro‐inflammatory cytokine mRNA expression.  相似文献   

20.
Since companion dogs have the same living environment as humans, they are a good animal model for the study of human diseases; this is especially true of canine spontaneous mammary tumours models. A better understanding of the natural history and molecular mechanisms of canine mammary tumour is of great significance in comparative medicine. Here, we collected canine mammary tumour cases and then assayed the clinical cases by pathological examination and classification by HE staining and IHC. miRNA‐497 family members (miR‐497, miR‐16, miR‐195 and miR‐15) were positively correlated with the breast cancer marker genes p63 and PTEN. Modulation of the expression of miR‐497 in the canine mammary tumour cell lines CMT1211 and CMT 7364 induced apoptosis and inhibited cell proliferation. Mechanistically, IRAK2 was shown to be a functional target of miR‐497 that affects the characteristics of cancer cells by inhibiting the activity of the NF‐κB pathway. Overall, our work reveals the miR‐497/IRAK2/NF‐κB axis as a vital mechanism of canine mammary tumour progression and suggests this axis as a target in breast cancer.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号