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1.
Adv Exp Med Biol ; 1185: 57-62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31884589

RESUMO

Geographic atrophy (GA), the advanced form of AMD, has been linked to oxidative stress within the RPE and with low-grade inflammation. The RPE-specific Sod2 knockout mouse model of GA develops increase oxidative stress and slow retinal degeneration. Mice of the SOD2floxed::VMD2Cre+ genotype were injected subcutaneously with either saline or 3 mg/kg of lipopolysaccharide (LPS) at 8 weeks of age. Mice were evaluated by electroretinography (ERG) and spectral domain optical coherence tomography. Inflammatory cells within the retina were studied by CD45 immunofluorescence. Systemic low-dose LPS transiently, but significantly, improved both function and structure of RPE-specific Sod2 KO mice retina when compared to saline-injected mice. There was no difference in CD45 positive cells between saline and LPS treatment. Low-grade activation of the immune system leads to a preconditioning effect that transiently protects the retina of a mouse model of geographic atrophy.


Assuntos
Atrofia Geográfica/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Animais , Eletrorretinografia , Injeções Subcutâneas , Lipopolissacarídeos/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Superóxido Dismutase , Tomografia de Coerência Óptica
2.
BMC Oral Health ; 19(1): 236, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684930

RESUMO

BACKGROUND: Antiinflammatory effect of 1,25-dihydroxyvitamin D3 (1,25D3) has been reported in periodontitis, but the exact mechanisms remain unclear. Oral epithelial cells are recently highlighted as an important regulator of inflammation in this disease. This in vitro study was established to investigate the effect of 1,25D3 on key proinflammatory cytokine IL-6 production and aryl hydrocarbon receptor (AhR)/nuclear factor-κB (NF-κB) signaling in oral epithelial cells upon the stimulation of lipopolysaccharide (LPS) from periodontal pathogens. METHODS: OKF6/TERT-2 oral keratinocytes were incubated with LPS and different concentrations of 1,25D3, and levels of IL-6 production were determined using enzyme-linked immunosorbent assay (ELISA). Expression of vitamin D receptor (VDR), and activation of AhR was examined using western blot analysis, and phosphorylation of NF-κB was detected using cell-based protein phosphorylation ELISA. RESULTS: 1,25D3 inhibited LPS-induced IL-6 overexpression in OKF6/TERT-2 cells. Additionally, 1,25D3 increased VDR expression and AhR activation, and repressed NF-κB phosphorylation. Furthermore, 1,25D3 suppressed IL-6 expression and enhanced VDR expression and regulated AhR/NF-κB signaling activation in a dose-dependent manner after 48 h treatment. CONCLUSIONS: These results suggest that 1,25D3 may inhibit LPS-induced IL-6 overexpression in human oral epithelial cells through AhR/NF-κB signaling. Our findings may provide an explanation for the antiinflammatory effect and therapeutic benefit of 1,25D3 in periodontitis.


Assuntos
Colecalciferol/administração & dosagem , Células Epiteliais , Interleucina-6/metabolismo , Interleucina-8/metabolismo , NF-kappa B/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico , Vitamina D/análogos & derivados , Humanos , Interleucina-6/genética , Interleucina-8/genética , Lipopolissacarídeos/administração & dosagem , Vitamina D/farmacologia
3.
Drug Des Devel Ther ; 13: 3259-3268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571828

RESUMO

Background: Cigarette smoke (CS) results in chronic mucus hypersecretion and airway inflammation, contributing to COPD pathogenesis. Mucin 5B (MUC5B) and mucin 5 AC (MUC5AC) are major mucins implicated in COPD pathogenesis. Carbocisteine can reduce mucus viscosity and elasticity. Although carbocisteine decreased human elastase-induced MUC5AC expression in vitro and reduced MUC5AC expression that alleviated bacteria adhesion and improved mucus clearance in vivo, the roles of carbocisteine in inducing MUC5B expression in COPD remain unclear. Methods: To investigate the Muc5b/Muc5ac ratio and the gene and protein levels of Muc5b in COPD and carbocisteine intervention models. C57B6J mice were used to develop COPD model by instilling intratracheally with lipopolysaccharide on days 1 and 14 and were exposed to CS for 2 hr twice a day for 12 weeks. Low and high doses of carbocisteine 112.5 and 225 mg/kg/d, respectively, given by gavage administration were applied for the treatment in COPD models for the same duration, and carboxymethylcellulose was used as control. Carbocisteine significantly attenuated inflammation in bronchoalveolar lavage fluid and pulmonary tissue, improved pulmonary function and protected against emphysema. Results: High-dose carbocisteine significantly decreased the overproduction of Muc5b (P<0.01) and Muc5ac (P<0.001), and restored Muc5b/Muc5ac ratio in COPD model group (P<0.001). Moreover, the Muc5b/Muc5ac ratio negatively correlated with pro-inflammatory cytokines such as IL-6 and keratinocyte-derived cytokine, mean linear intercept, functional residual capacity and airway resistance, but positively correlated with dynamic compliance. Conclusions: These findings suggest that carbocisteine attenuated Muc5b and Muc5ac secretion and restored Muc5b protein levels, which may improve mucus clearance in COPD.


Assuntos
Carbocisteína/uso terapêutico , Mucina-5AC/metabolismo , Mucina-5B/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Quimiocinas/metabolismo , Fumar Cigarros/efeitos adversos , Modelos Animais de Doenças , Enfisema/prevenção & controle , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/administração & dosagem , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Muco/metabolismo , Doença Pulmonar Obstrutiva Crônica/imunologia
4.
J Anim Sci ; 97(11): 4475-4481, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31560759

RESUMO

Newly weaned, commercial Angus steers [body weight (BW) = 204 ± 19 kg; n = 24; 12 steers from dams administered an injectable trace mineral (MM; Mulimin90) and 12 steers from control (CON) dams] were utilized to determine the effects of maternal supplementation with an injectable trace mineral on the inflammatory response of subsequent steers subjected to a lipopolysaccharide (LPS) challenge at the initiation of a 42-d receiving period. On day -2 steers were weaned, and the following day, shipped 354 km to the Beef Cattle and Sheep Field Laboratory in Urbana, IL. On day 0, steers were administered an intravenous LPS challenge. Body temperature and blood samples were collected from steers prior to LPS administration (0 h) and again at 0.5, 1, 2, 3, 4, 5, and 6 h. Blood samples were analyzed for trace mineral and cortisol at 0 and 2 h and glucose, insulin, LPS-binding protein (LBP), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), haptoglobin, ceruloplasmin, and fibrinogen at 0, 0.5, 1, 2, 3, 4, 5, and 6 h. Calf BW was collected at trial initiation and subsequently every 14 d. Dry matter intake was collected daily and average daily gain (ADG) and feed efficiency were assessed. Initial plasma Zn tended (P = 0.06) to be greater for MM steers. However, there was no difference (P ≥ 0.31) in trace mineral status or serum cortisol at any other time. Total area under the curve (TAUC) for body temperature was lesser (P > 0.01) for MM steers. Basal LBP concentrations and TAUC for LBP tended (P ≤ 0.10) to be greater for MM steers. Peak concentration of IL-6 tended (P = 0.09) to be reached earlier for CON steers. However, there was no difference (P ≥ 0.11) in glucose, insulin, IL-6, ceruloplasmin, haptoglobin, and fibrinogen concentrations between treatments. Calf performance and feed efficiency did not differ (P ≥ 0.17) between treatments except ADG from day 28 to 42, which was greater (P = 0.03) for CON steers. Maternal supplementation with an injectable trace mineral tended to improve steer plasma Zn status at 0 h and tended to increase basal concentrations of LBP and overall LBP production when steers were administered an LPS challenge. Additionally, MM steers exhibited a more favorable change in body temperature following LPS administration. However, injectable trace mineral supplementation of dams during gestation had minimal to no effect on cytokine and acute-phase protein concentrations, as well as overall calf performance and efficiency during a 42-d receiving period.


Assuntos
Bovinos/fisiologia , Suplementos Nutricionais/análise , Inflamação/veterinária , Oligoelementos/administração & dosagem , Ração Animal/análise , Animais , Peso Corporal/efeitos dos fármacos , Dieta/veterinária , Feminino , Hidrocortisona/sangue , Inflamação/prevenção & controle , Lipopolissacarídeos/administração & dosagem , Masculino , Gravidez , Ovinos , Oligoelementos/sangue
5.
Int J Mol Sci ; 20(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370360

RESUMO

BACKGROUND: Gadolinium chloride (GdCl3) has been reported to attenuate liver injury caused by a variety of toxicants. Gap junctional intercellular communication (GJIC) is thought to be essential in controlling liver homeostasis and pathology. Here we evaluate the effects of GdCl3 on functional GJIC and connexin expression in mouse models and primary hepatocytes. METHODS: Mice were administered GdCl3 intraperitoneally the day before a carbon tetrachloride (CCl4) injection or bile duct ligation (BDL) operation. Primary hepatocytes were treated with CCl4 or lipopolysaccharides (LPS), with or without GdCl3. A scrape loading/dye transfer assay was performed to assess the GJIC function. The expression of connexins was examined by real-time reverse transcription polymerase chain reaction (RT-PCR), western blot and immunofluorescent staining. RESULTS: CCl4 treatment or the BDL operation led to the dysfunction of GJIC and a down-regulation of Cx32 and Cx26 in injured liver. GdCl3 administration restored GJIC function between hepatocytes by facilitating the transfer of fluorescent dye from one cell into adjacent cells via GJIC, and markedly prevented the decrease of Cx32 and Cx26 in injured liver. In primary hepatocytes, CCl4 or LPS treatment induced an obvious decline of Cx32 and Cx26, whereas GdCl3 pretreatment prevented the down-regulation of connexins. In vivo GdCl3 protected hepatocytes and attenuated the liver inflammation and fibrosis in liver injury mouse models. CONCLUSION: GdCl3 administration protects functional GJIC between hepatocytes, and prevents the decrease of connexin proteins at mRNA and protein levels during liver injury, leading to the alleviation of chronic liver injury.


Assuntos
Anti-Inflamatórios/farmacologia , Comunicação Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Gadolínio/farmacologia , Junções Comunicantes/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Ductos Biliares/cirurgia , Tetracloreto de Carbono/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Conexinas/agonistas , Conexinas/genética , Conexinas/metabolismo , Regulação da Expressão Gênica , Hepatócitos/metabolismo , Hepatócitos/patologia , Ligadura , Lipopolissacarídeos/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Cultura Primária de Células
6.
Vet Immunol Immunopathol ; 215: 109914, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31420065

RESUMO

This pilot study provides a preliminary assessment of the impact of genotype on acute innate immune pro-inflammatory, metabolic and endocrine responses to repeated lipopolysaccharide (LPS) administered to growing heifers. Heifers (n = 4/genotype) were from unselected (stable milk yield since 1964, UH) or contemporary (CH) Holstein cows that differed in milk yield (6200 vs 11,100 kg milk/305 d) or from contemporary Black Angus (CA) cows bred to contemporary Red Angus bulls. Heifers were challenged with iv administration of 0.5 µg LPS/kg body weight on day 1 (Challenge 1) and d 5 (Challenge 2) of study to assess endotoxin tolerance. Plasma was collected at -1, -0.5, 0, 1, 2, 3, 4, 6, 8, and 24 h relative to each LPS administration. Rectal body temperature (BT) was measured before each blood sampling and at 5 and 7 h. Data were analyzed by repeated measures with sampling time as the repeated effect. Each genotype had at least one pro-inflammatory response that indicated it might have a more robust response than the other genotypes. The CH heifers had a greater TNF-α response, UH heifers had greater IL-6 and XO responses and CA heifers had greater BT and SAA response to LPS than the other genotypes. There was a genotype by time by interaction as cortisol peaked earlier in CH and UH than in CA heifers. Glucose response was less in CA and insulin response was greater in CH heifers. Endotoxin tolerance to LPS was evident as pro-inflammatory, cortisol, glucose and insulin responses were less during Challenge 2 than during Challenge 1. Differences among genotypes during Challenge 1 were eliminated during Challenge 2 except for the greater SAA response in CA heifers and indicate the potential for differential impacts of genotype on the development of endotoxin tolerance. Specific reasons for these effects of genotype are not clear from these data but the results support the hypothesis for differential innate immune signaling among these bovine genotypes.


Assuntos
Bovinos/imunologia , Imunidade Inata/genética , Animais , Bovinos/genética , Doenças dos Bovinos/imunologia , Indústria de Laticínios , Feminino , Genótipo , Inflamação/imunologia , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Projetos Piloto
7.
Anticancer Res ; 39(8): 4503-4509, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366552

RESUMO

BACKGROUND/AIM: Oral administration of Pantoea agglomerans-derived lipopolysaccharide (LPSp) has been reported to have a preventive effect against various lifestyle-related diseases. Therefore, we examined the preventive effect on high blood pressure, which is a kind of reserve arm for lifestyle-related diseases. MATERIALS AND METHODS: Spontaneous hypertensive rat (SHR) and WKY rat were bred from 6 to 16 weeks of age. SHR were orally administered 100 µg/kg LPSp and 0.1% NaCl, and blood pressure was measured at 6, 10, 13 and 16 weeks. Furthermore, at 16 weeks of age, blood biochemical markers were measured and microbial community composition was analyzed. RESULTS: SHRs developed hypertension with age, which was exacerbated by salt loading. Although there was almost no reduction in blood pressure in SHRs that received LPSp. It was suppressed at 13-16 weeks of age in those with salt loading. CONCLUSION: Oral administration of LPSp showed a preventive effect on salt-loaded hypertension.


Assuntos
Citocinas/genética , Hipertensão/tratamento farmacológico , Lipopolissacarídeos/administração & dosagem , Pantoea/química , Administração Oral , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Hipertensão/genética , Hipertensão/patologia , Lipopolissacarídeos/química , Masculino , Fagocitose/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Sais/toxicidade
8.
Immunopharmacol Immunotoxicol ; 41(5): 521-526, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31429348

RESUMO

Background: Interleukin (IL)-18 is a pro-inflammatory cytokine that has important functions in host defense. The maturation and secretion of IL-18 has been shown to be regulated by the NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome. Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), in association with lipopolysaccharide (LPS), is able to promote the secretion of IL-18, but the mechanism remains unknown. This study aims to explore the mechanism by which MPA synergizes with LPS to induced IL-18 release. Methods: THP-1 cells were stimulated with LPS and MPA and treated with or without the inhibitors of caspase-1, Ac-YVAD-cmk or KCl; IL-18 in the supernatants was measured by ELISA. The intracellular protein levels of NF-κB p-p65, pro-IL-18, NLRP3, and cleaved caspase-1(p20) were measured by Western blot. Results: We found that MPA alone failed to induce IL-18, whereas MPA enhanced LPS-mediated IL-18 release. MPA did not affect the intracellular protein levels of NF-κB p-p65 or pro-IL-18 but activated the NLRP3 inflammasome. Ac-YVAD-cmk or increasing extracellular K+ blocked the activation of caspase-1 and attenuated the release of IL-18. Conclusions: Taken together, MPA synergized with LPS to induce the release of IL-18 via activating the NLRP3 inflammasome and increasing the degradation of pro-IL-18, rather than by enhancing the production of pro-IL-18.


Assuntos
Inflamassomos/metabolismo , Interleucina-18/metabolismo , Lipopolissacarídeos/farmacologia , Ácido Micofenólico/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sinergismo Farmacológico , Humanos , Lipopolissacarídeos/administração & dosagem , Ácido Micofenólico/administração & dosagem , Células THP-1
9.
Vet Res Commun ; 43(4): 225-230, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31446518

RESUMO

Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) that mediate first line of host defence to pathogens. TLR agonists are potent immunostimulatory agents that help to prime a robust adaptive immune response. In the present study, adjuvant potential of Poly I:C and lipopolysaccharide (LPS) were evaluated with live Newcastle disease virus (NDV) vaccine. Cornish chickens were immunized with live Newcastle disease virus (NDV) vaccine (R2B-mesogenic strain) adjuvanted either with Poly I:C (TLR3 agonist) or LPS-TLR4 agonist and both. Humoral Immune response to ND vaccine was evaluated through haemagglutination inhibition (HI) test and ELISA, while the cellular immune response (CMI) was quantified by lymphocyte transformation test (LTT). IL-1ß cytokine mRNA levels in spleen tissue were also quantified by real time PCR. The results suggest that TLR3 and TLR4 agonists are an efficient immune-stimulators separately, as LPS co-administered group has shown significantly higher serum titre on second week post-immunization and Poly I:C group on third week post-immunization both by HI and ELISA (P < 0.01), however, the combined administration of both LPS and Poly I:C did not give any complementary effect on serum titre. There were no significant differences in stimulation indices (SI) and IL-1ß cytokine levels between groups at different intervals post-immunization. Hence, TLR agonists LPS followed by Poly I:C could be used as adjuvant to enhance the immune response to NDV vaccine in chicken.


Assuntos
Imunidade Humoral/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Doença de Newcastle/imunologia , Poli I-C/farmacologia , Receptor 3 Toll-Like/agonistas , Receptor 4 Toll-Like/agonistas , Vacinas Virais/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Animais , Galinhas , Ensaio de Imunoadsorção Enzimática , Imunidade Celular/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Vírus da Doença de Newcastle/imunologia , Poli I-C/administração & dosagem
10.
Pharm Biol ; 57(1): 555-563, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31446815

RESUMO

Context: Lipopolysaccharide (LPS) is often used to induce immunoinflammatory reactions. TLR4/NFκB and NLRP3 signalling are major factors for inflammation. Dexamethasone (DXM) has an anti-immunoinflammatory effect. Objective: To investigate the inflammatory reaction in pathological changes of organs and the expression of inflammatory signalling during LPS infection. Materials and methods: ICR mice were divided into control group (n = 9), LPS group (n = 15) and LPS + DXM group (n = 14). LPS (10 mg/kg) was injected intravenously in LPS group and LPS + DXM group, normal saline was injected to the control group; DXM (0.5 mg/kg) was given by intragastric administration. 12 h after LPS, the blood was collected and the organs were isolated for biochemical analysis, protein expression, and morphological examination. Results: The results showed that BUN, Cre, ALT, AST in the LPS group increased distinctly by 81.42, 67.84, 40.53 and 36.05%, respectively, and CK, ALP, TP and ALB decreased by 71.37, 60.6, 12.57 and 19.73%, respectively, compared with the control group. In the morphologic observation, local necrosis in the liver, arterial vasodilation in the heart and kidney, alveolar secretions and pulmonary interstitial in the lungs, and mucosal shedding in the small and large intestines, the expression of TLR4-NFκB signalling were up-regulated distinctly whereas NLRP3 signalling was less broadly affected. DXM can decrease BUN and Cre, downregulate the expression of TLR4-NFκB signalling, but has no effect on the organ damage based on morphology. Conclusion: Acute injuries induced by LPS are extensive. The inflammatory damage in small and large intestines, liver and kidney was more severe than other organs. TLR4-NFκB signalling was the major response to LPS stress.


Assuntos
Intestinos/efeitos dos fármacos , Rim/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Biomarcadores/sangue , Inflamação , Injeções Intravenosas , Intestinos/imunologia , Rim/imunologia , Rim/metabolismo , Lipopolissacarídeos/administração & dosagem , Fígado/imunologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Transdução de Sinais
11.
Int Immunopharmacol ; 75: 105751, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31319359

RESUMO

Methamphetamine (METH) is a stimulant of the central nervous system (CNS) that causes behavioral changes in users. METH is slowly cleared from brain tissue and its chronic use is neurotoxic. METH also alters the cellular and chemical components of inflammation. However, little is known about the effect of a single intravenous dose of METH followed by bacterial lipopolysaccharide (LPS) injection on cellular infiltration and cytokine release in brain tissue. Using a murine model of acute METH administration and flow cytometry, we found that combination of METH and LPS stimulate the infiltration of macrophages (F4/80+cells) and neutrophils (Ly-6G+cells) into the CNS. Histological sections of the brainstem of METH-treated and LPS-challenged C57BL/6 mice demonstrated considerable leukocyte infiltration relative to untreated, LPS, and METH groups. Moreover, rodents treated with LPS alone or combined with METH showed elevated levels of pro-inflammatory cytokines mRNA in brain tissue. Our observations are important because recognizing neuroinflammatory changes after acute METH administration might help us to understand METH-induced neurotoxicity in users.


Assuntos
Encéfalo/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Leucócitos/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Metanfetamina/administração & dosagem , Animais , Encéfalo/imunologia , Citocinas/genética , Citocinas/imunologia , Feminino , Injeções Intravenosas , Leucócitos/imunologia , Masculino , Camundongos Endogâmicos C57BL
12.
Res Vet Sci ; 125: 290-297, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31349186

RESUMO

Endotoxemia treatment options are still of interest due to high mortality and choline treatment is one of them because of its role in the cholinergic anti-inflammatory pathway. This study investigated serum choline and butyrylcholinesterase (BChE) responses, and their correlations with inflammatory, oxidative stress and tissue damage biomarkers, including paraoxanase-1 (PON1), and clinical signs in calves with endotoxemia and the effect of choline treatment in these responses. Healthy calves (n = 20) were divided equally into 4 groups: Control (0.9% NaCl, iv), Choline (C; 1 mg/kg/iv,once), Lipopolysaccharide (LPS; 2 µg/kg/iv,once) and LPS + C. Clinical and laboratory examinations were performed before and 0.5-48 h (hrs) after treatments. Following LPS administration, serum choline level increased at 0.5-24 h (P < .01), whereas serum BChE and PON1 level decreased at 48 h (P < .01) compared to their baselines. In LPS + C group, the increase in serum choline level was significantly higher (P < .01) than that of C and LPS groups. LPS did not decrease serum BChE levels significantly in calves treated with choline. Serum choline and BChE results correlated negatively with white blood cell count and positively (P < .001) with PON1 levels, oxidative stress index, inflammation and hepato-muscular injury markers. In conclusion serum choline and BChE may have a role in the pathophysiology of endotoxemia in calves. High serum choline concentration is associated with an improvement in response to LPS administration in calves treated with choline, probably by preventing the imbalances between oxidative stress and anti-oxidant capacity, preventing the serum BChE and PON1 decreases, and inhibition/attenuation of acute phase reaction and hepato-muscular injury in calves with endotoxemia.


Assuntos
Butirilcolinesterase/sangue , Doenças dos Bovinos/induzido quimicamente , Colina/sangue , Endotoxemia/veterinária , Lipopolissacarídeos/toxicidade , Reação de Fase Aguda/tratamento farmacológico , Administração Intravenosa , Animais , Biomarcadores/sangue , Butirilcolinesterase/metabolismo , Bovinos , Doenças dos Bovinos/sangue , Doenças dos Bovinos/tratamento farmacológico , Endotoxemia/tratamento farmacológico , Endotoxemia/fisiopatologia , Inflamação/tratamento farmacológico , Contagem de Leucócitos , Lipopolissacarídeos/administração & dosagem , Masculino , Estresse Oxidativo , Distribuição Aleatória
13.
J Anim Sci ; 97(10): 4140-4151, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31310662

RESUMO

This study was conducted to investigate the effects of Clostridium butyricum and Enterococcus faecalis on growth performance, immune function, inflammation-related pathways, and microflora community in weaned piglets challenged with lipopolysaccharide (LPS). One hundred and eighty 28-d-old weaned piglets were randomly divided into 3 treatments groups: piglets fed with a basal diet (Con), piglets fed with a basal diet containing 6 × 109 CFU C. butyricum·kg-1 (CB), and piglets fed with a basal diet containing 2 × 1010 CFU E. faecali·kg-1 (EF). At the end of trial, 1 pig was randomly selected from for each pen (6 pigs per treatment group) and these 18 piglets were orally challenged with LPS 25 µg·kg-1 body weight. The result showed that piglets fed C. butyricum and E. faecalis had greater final BW compared with the control piglets (P < 0.05). The C. butyricum and E. faecalis fed piglets had lower levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), IL-1ß, tumor inflammatory factor-α (TNF-α), and had greater level of serum interferon-γ (IFN-γ) than control piglets at 1.5 and 3 h after injection with LPS (P < 0.05). Furthermore, piglets in the C. butyricum or E. faecalis treatment groups had a greater ratio of jejunal villus height to crypt depth (V/C) compared with control piglets after challenge with LPS for 3 h (P < 0.05). Compared with the control treatment, the CB and EF treatments significantly decreased the expression of inflammation-related pathway factors (TLR4, MyD88, and NF-κB) after challenge with LPS for 3 h (P < 0.05). High-throughput sequencing revealed that C. butyricum and E. faecalis modulated bacterial diversity in the colon. The species richness and alpha diversity (Shannon) of bacterial samples in CB or EF piglets challenged with LPS were higher than those in LPS-challenged control piglets. Furthermore, the relative abundance of Bacteroidales-Rikenellanceae in the CB group was higher than that in the control group (P < 0.05), whereas EF piglets had a higher relative abundance of Lactobacillus amylovorus and Lactobacillus gasseri (P < 0.05). In conclusion, dietary supplementation with C. butyricum or E. faecalis promoted growth performance, improved immunity, relieved intestinal villus damage and inflammation, and optimized the intestinal flora in LPS-challenged weaned piglets.


Assuntos
Ração Animal/análise , Clostridium butyricum/fisiologia , Enterococcus faecalis/fisiologia , Microbioma Gastrointestinal , Probióticos/análise , Suínos/fisiologia , Animais , Dieta/veterinária , Inflamação/veterinária , Mucosa Intestinal/microbiologia , Intestinos/microbiologia , Lactobacillus/crescimento & desenvolvimento , Lipopolissacarídeos/administração & dosagem , Distribuição Aleatória , Suínos/crescimento & desenvolvimento , Suínos/imunologia , Suínos/microbiologia
14.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(6): 682-685, 2019 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-31238619

RESUMO

Objective: To explore the effect of lipopolysaccharide intervention program on Legionella pneumonia. Methods: C3H/HeN mice (6-8 weeks old) were used as experimental animals. The mice were randomly divided into lipopolysaccharide intervention, non-lipopolysaccharide intervention and control groups. Each group was again divided into three time points: 12 h, 24 h and 48 h. Mice in the lipopolysaccharide intervention group were intraperitoneally injected with E. coli lipopolysaccharide (100 ng per mice), and the rest groups were intraperitoneally injected with normal saline. After 24 hours, mice in the lipopolysaccharide intervention and the non-intervention groups mice were infected with Legionella by tracheal injection and the control group was given the same amount of saline. All the mice were killed at 12, 24 and 48 hours respectively. The mice were anatomized, lungs of the mice were separated and weighed. Organ coefficients (lung weight/body weight of mice) were calculated. 1 ml Orbital blood was collected. Toll-like receptor 4 (TLR4) levels of peripheral blood mononuclear cells were measured by flow cytometry. The contents of TNF-α and IL-1ß in the upper left lung lobe were measured by ELISA. Results: In the lung organs, the coefficients of lipopolysaccharide non-intervention group were higher than the other groups and there was no significant difference seen between the lipopolysaccharide intervention group and the controls. TLR4 peaked at 12 hours in both the lipopolysaccharide intervention and the non-intervention groups while the TLR4 level in the intervention group was higher than that in the non-intervention group. There were no significant differences appeared on the TLR4 expression levels between the two Legionella pneumonia modelled groups at 24 or 48 hours. There was no significant difference seen regarding the concentration of TNF-α and IL-1ß between the intervention and the control groups. The secretion levels of TNF-α and IL-1ß in the non-intervention group were higher than those in the intervention group at each time point. Conclusion: The lipopolysaccharide intervention program may alleviate the inflammatory symptoms of Legionella infection.


Assuntos
Legionella , Lipopolissacarídeos/farmacologia , Pneumonia , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Experimentação Animal , Animais , Escherichia coli , Leucócitos Mononucleares , Lipopolissacarídeos/administração & dosagem , Camundongos , Camundongos Endogâmicos C3H , Distribuição Aleatória
15.
J Anim Sci ; 97(8): 3354-3368, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31250878

RESUMO

The aim of this study was to evaluate the associated effects of ambient temperature and inflammation caused by repeated administration of Escherichia coli lipopolysaccharide (LPS) on insulin, energy, and AA metabolism. Twenty-eight pigs were assigned to one of the two thermal conditions: thermoneutral (24 °C) or high ambient temperature (30 °C). The experimental period lasted 17 d, which was divided into a 7-d period without LPS (days -7 to -1), and a subsequent 10-d LPS period (days 1 to 10) in which pigs were administered 5 repeated injections of LPS at 2-d intervals. Postprandial profiles of plasma insulin and nutrients were evaluated through serial blood samples taken on days -4 (P0), 4 (P1), and 8 (P2). Before the LPS-challenge (P0), postprandial concentrations of glucose, lactate, Gln, Ile, Leu, Phe, Tyr, and Val were greater in pigs kept at 24 °C than at 30 °C (P < 0.05). In contrast, Arg, Asp, Gly, His, and Met postprandial concentrations at P0 were lower at 24 °C than at 30 °C (P < 0.05). At both 24 and 30 °C conditions, pigs had greater postprandial concentrations of insulin (P < 0.01) and lower concentrations of NEFA (P < 0.01) and α-amino nitrogen (P < 0.05) at P1 and P2 than at P0. Compared with P0, postprandial concentrations of glucose were greater (P < 0.05) at P1 in pigs kept at 24 °C, and at P1 and P2 in pigs kept at 30 °C. At both ambient temperatures, pigs had lower (P < 0.05) postprandial concentrations of Ala, Gly, His, Ile, Leu, Pro, Ser, Thr, Trp, and Val at P1 and P2 than at P0. Arginine postprandial concentration at P1 was lower than at P0 in pigs kept at 24 °C (P < 0.05), whereas no difference was observed in pigs at 30 °C. Relative to P0, Gln and Tyr concentrations were lower at P1 and P2 in pigs kept at 24 °C (P < 0.01), whereas lower Gln concentration was observed only at P2 (P < 0.01) and lower Tyr only at P1 (P < 0.01) in pigs kept at 30 °C. Our study shows a hyperglycemic and hyperinsulinemic state in LPS-challenged pigs and a greater magnitude of this response in pigs kept at 30 °C. Furthermore, LPS caused important changes in BCAA, His, Thr, and Trp profiles, suggesting the role these AA in supporting the inflammatory response. Finally, our results suggest that LPS-induced effects on postprandial profiles of specific AA (Arg, Gln, Phe, and Tyr) may be modulated by ambient temperature.


Assuntos
Aminoácidos/sangue , Metabolismo Energético , Insulina/sangue , Nutrientes/sangue , Suínos/fisiologia , Animais , Escherichia coli/química , Resposta ao Choque Térmico , Temperatura Alta , Inflamação/veterinária , Lipopolissacarídeos/administração & dosagem , Nitrogênio/sangue , Período Pós-Prandial , Estresse Fisiológico , Suínos/sangue
16.
Yakugaku Zasshi ; 139(9): 1211-1217, 2019 Sep 01.
Artigo em Japonês | MEDLINE | ID: mdl-31189750

RESUMO

Corticosteroid insensitive airway inflammation is one of major barrier to effective managements of chronic airway diseases, such as chronic obstructive pulmonary disease (COPD) and severe asthma. The role of nonreceptor tyrosine kinase Src is important in airway inflammation in mice models of atopic asthma and COPD. Thus, in this study, we determined the effects of Src inhibitor, dasatinib, on airway inflammation induced by repeated intranasal exposure to lipopolysaccharide (LPS). Male mice (A/J strain, 5 weeks old) were intranasally exposed to LPS twice daily for 3 d, and dasatinib was intranasally treated 2 h prior to each LPS exposure. A day after the last stimulation, lungs and bronchoalveolar lavage fluid (BALF) were collected. Dasatinib attenuated the accumulation of inflammatory cells in lungs, and the increase in the numbers of inflammatory cells and the accumulation of cytokines/chemokines in BALF in a dose dependent manner. Therefore, this study suggested that targeting the Src can provide a new therapeutic approach for corticosteroid insensitive pulmonary diseases.


Assuntos
Asma/tratamento farmacológico , Dasatinibe/administração & dosagem , Dasatinibe/farmacologia , Lipopolissacarídeos/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/fisiologia , Administração Intranasal , Corticosteroides , Animais , Asma/induzido quimicamente , Asma/metabolismo , Líquido da Lavagem Broncoalveolar/química , Quimiocinas/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Inflamação , Lipopolissacarídeos/administração & dosagem , Masculino , Camundongos Endogâmicos , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/metabolismo , Índice de Gravidade de Doença
17.
J Anim Sci ; 97(7): 2940-2951, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31081510

RESUMO

The present study used Escherichia coli lipopolysaccharide (LPS) to investigate whether maternal immune challenge during late gestation altered programming of the offspring hypothalamus and hypothalamic-pituitary-adrenal axis (HPAA). In addition, interactions of maternal diet, supplementation with fish oil (FO) or microalgae (AL), and complex vs. simple weaning diets were investigated. Briefly, Landrace × Yorkshire sows (N = 48) were randomly assigned to diets supplemented with FO, AL, or a standard gestation control diet (CON) from day 75 of gestation (gd 75) until parturition. On gd 112, half the sows from each dietary treatment were immune challenged with LPS (10 µg/kg BW) or saline as a control. At 21 d postpartum, the offspring were weaned, and half the animals from each maternal treatment were allocated to either a complex or simple weaning diet. At 28 d postpartum, the offspring's hourly fever and 2-h cortisol responses to LPS immune challenge (40 µg/kg BW) were measured to assess hypothalamus and HPAA function. Results indicated that the maternal temperature of sows on the FO diet returned to baseline levels faster than sows on the AL and CON diets after LPS immune challenge (P < 0.05). In contrast, there was no difference in the maternal cortisol response across the dietary treatments (P > 0.10). Regardless of the dietary treatments, the maternal LPS immune challenge induced a greater cortisol response in male offspring (P = 0.05) and a greater fever response in female offspring (P = 0.03) when they were LPS immune challenged post-weaning. Male offspring from LPS-immune-challenged sows fed the FO and AL diets had a greater fever response than male offspring from the maternal CON diet group (P ≤ 0.05). Last, no effect of the complex or simple weaning diets was observed for the nursery pig cortisol or fever responses to LPS immune challenge. In conclusion, LPS immune challenge during late pregnancy altered responsiveness of the offspring hypothalamus and HPAA to this same microbial stressor, and a sex-specific response was influenced by maternal dietary supplementation with FO and AL.


Assuntos
Suplementos Nutricionais , Óleos de Peixe/farmacologia , Microalgas , Suínos/fisiologia , Animais , Óleo de Milho/farmacologia , Dieta/veterinária , Escherichia coli/química , Feminino , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Lipopolissacarídeos/administração & dosagem , Masculino , Projetos Piloto , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Distribuição Aleatória , Fatores Sexuais , Suínos/imunologia , Desmame
18.
Nat Commun ; 10(1): 1999, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31040289

RESUMO

Mononuclear phagocytes (MPs) including monocytes, macrophages and dendritic cells (DCs) are critical innate immune effectors and initiators of the adaptive immune response. MPs are present in the alveolar airspace at steady state, however little is known about DC recruitment in acute pulmonary inflammation. Here we use lipopolysaccharide inhalation to induce acute inflammation in healthy volunteers and examine the impact on bronchoalveolar lavage fluid and blood MP repertoire. Classical monocytes and two DC subsets (DC2/3 and DC5) are expanded in bronchoalveolar lavage fluid 8 h after lipopolysaccharide inhalation. Surface phenotyping, gene expression profiling and parallel analysis of blood indicate recruited DCs are blood-derived. Recruited monocytes and DCs rapidly adopt typical airspace-resident MP gene expression profiles. Following lipopolysaccharide inhalation, alveolar macrophages strongly up-regulate cytokines for MP recruitment. Our study defines the characteristics of human DCs and monocytes recruited into bronchoalveolar space immediately following localised acute inflammatory stimulus in vivo.


Assuntos
Células Dendríticas/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Macrófagos Alveolares/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Humanos , Lipopolissacarídeos/administração & dosagem
19.
Acta Neurobiol Exp (Wars) ; 79(1): 73-85, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038486

RESUMO

Preconditioning with lipopolysaccharide (LPS) or opioid antagonists has a neuroprotective effect in ischemic insults. However, the co­preconditioning effect of toll­like receptor ligands and opioid antagonists has not been investigated. In this study we examined the neuroprotective effect of LPS and naltrexone (NTX) preconditioning and co­preconditioning in unilateral selective hippocampal ischemia in rats to assess for possible synergistic protective effects. LPS and NTX were injected unilaterally into the left cerebral ventricle of male rats. Forty­eight hours after LPS and twenty­four hours after NTX injection, ipsilateral selective hippocampal ischemia was induced using a modified version of the photothrombotic method. Protective effects for LPS and NTX were assessed by evaluating infarct volume (using 2,3,5­triphenyltetrazolium chloride staining), and cognitive function (using radial arm water maze and passive avoidance tests). Animals in the ischemic group had an infarct lesion and considerable cognitive impairment, compared with the sham group. LPS or NTX preconditioning significantly reduced the infarct size and improved cognitive function. Moreover, co­preconditioning with LPS and NTX increased the protective effect compared with preconditioning with LPS or NTX alone. Our data showed that LPS and NTX preconditioning resulted in a neuroprotective effect in hippocampal ischemia. Furthermore, co­preconditioning with LPS and NTX resulted in a synergistic protective effect.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Lateralidade Funcional/fisiologia , Hipocampo/patologia , Precondicionamento Isquêmico/métodos , Lipopolissacarídeos/administração & dosagem , Naltrexona/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Isquemia Encefálica/complicações , Isquemia Encefálica/etiologia , Modelos Animais de Doenças , Hipocampo/irrigação sanguínea , Injeções Intraventriculares , /prevenção & controle , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Estimulação Luminosa/efeitos adversos , Distribuição Aleatória , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Resultado do Tratamento
20.
Nat Commun ; 10(1): 2126, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31073164

RESUMO

Repair of the endothelial cell barrier after inflammatory injury is essential for tissue fluid homeostasis and normalizing leukocyte transmigration. However, the mechanisms of endothelial regeneration remain poorly understood. Here we show that the endothelial and hematopoietic developmental transcription factor Sox17 promotes endothelial regeneration in the endotoxemia model of endothelial injury. Genetic lineage tracing studies demonstrate that the native endothelium itself serves as the primary source of endothelial cells repopulating the vessel wall following injury. We identify Sox17 as a key regulator of endothelial cell regeneration using endothelial-specific deletion and overexpression of Sox17. Endotoxemia upregulates Hypoxia inducible factor 1α, which in turn transcriptionally activates Sox17 expression. We observe that Sox17 increases endothelial cell proliferation via upregulation of Cyclin E1. Furthermore, endothelial-specific upregulation of Sox17 in vivo enhances lung endothelial regeneration. We conclude that endotoxemia adaptively activates Sox17 expression to mediate Cyclin E1-dependent endothelial cell regeneration and restore vascular homeostasis.


Assuntos
Ciclina E/genética , Endotélio Vascular/fisiopatologia , Endotoxemia/patologia , Proteínas HMGB/metabolismo , Proteínas Oncogênicas/genética , Regeneração/imunologia , Fatores de Transcrição SOXF/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Ciclina E/metabolismo , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Endotoxemia/imunologia , Células HEK293 , Proteínas HMGB/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Oncogênicas/metabolismo , Regiões Promotoras Genéticas/genética , Fatores de Transcrição SOXF/genética , Transdução de Sinais/fisiologia , Regulação para Cima
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