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1.
NO is produced by macrophages through activation of the inducible enzyme NOS and its production is triggered as an antiviral and antitumoral immune mechanism. Replication of Marek's disease herpes virus (MDV) is inhibited by NO in vitro. MDV induces T-lymphomas in the chicken and a genetic resistance to tumor development has been linked to the B21 major histocompatibility complex. During the first initial week of viral replication after inoculation of the highly virulent RB-1B MDV strain, histocompatible B21/B21 chickens developed strong iNOS expression and NO production capacity in the spleen, in parallel with strong systemic NO production in the serum. Comparable NO response was not seen with the vaccinal strain HVT. In contrast, reduction in spleen macrophage number and delay in iNOS gene expression was observed in genetically susceptible B13/B13 chickens after MDV infection, in addition to suppression of IFN-gamma-inducible NO production. However, vaccination with HVT 3 days before RB-1B inoculation restored strong iNOS gene expression in the spleen 1 week later and inducible NO production 3 weeks later. Following the pattern of iNOS gene expression, early strong expression of cytokines with powerful iNOS-inducing activity such as IFN-gamma and CC chemokines from the MIP family (MIP-1beta, K203) was observed in genetic resistance and resistance acquired after vaccination with HVT. In conclusion, resistance to MDV appeared preferentially linked in both types of resistance to the early establishment of cytokine induction characteristic of a Th1 immune response, thus favoring the development of an early and strong NO response.  相似文献   

2.
Utilizing RNA interference technology with siRNA in the HD11 macrophage cell line, we determined how the inhibition or knock-down of the iNOS (inducible nitric oxide synthase) gene affected IFN-gamma-induced macrophage production of nitric oxide (NO) and mRNA expression of genes involved in this biological pathway in the chicken. Chicken macrophages produce NO when stimulated with recombinant chicken IFN-gamma, however, when transfected with iNOS siRNAs, the production of NO is significantly decreased. We observed a 14-28% reduction in NO production by IFN-gamma-stimulated HD11 cells at 48h after initial siRNA transfection compared to non-transfected IFN-gamma-stimulated macrophages. Significant knock-down of iNOS mRNA expression (15 to 50-fold lower) was observed for each of four iNOS siRNAs, when compared to non-transfected IFN-gamma-stimulated macrophages and to those treated with a negative control siRNA. The IFN-gamma-stimulated chicken macrophages transfected with iNOS siRNAs did not show altered levels of mRNA expression for genes involved in IFN-gamma signaling and iNOS pathways (IL-1beta, IL-6, IFN-gamma, TGF-beta4, or SOCS-3) suggesting that the observed decrease in NO production is a direct result of siRNA mediated knock-down of iNOS, rather than IFN-gamma-induced changes in the other genes tested.  相似文献   

3.
Lillehoj HS  Li G 《Avian diseases》2004,48(2):244-253
Nitric oxide (NO) is an important mediator of innate and acquired immunities. In the studies reported here, we quantified NO produced in vitro by chicken leukocytes and macrophages and in vivo during the course of experimental infection with Eimeria, the causative agent of avian coccidiosis, and identified macrophages as the primary source of inducible NO. Eimeria tenella-infected chickens produced higher levels of NO compared with noninfected controls. In Eimeria-infected animals, SC chickens produced greater amounts of NO compared with infected TK chickens, particularly in the intestinal cecum, the region of the intestine infected by E. tenella. Macrophages that were isolated from normal spleen were a major source of NO induced by interferon (IFN)-gamma, lipopolysaccharide (LPS), and E. tenella sporozoites. Macrophage cell line MQ-NCSU produced high levels of NO in response to Escherichia coli or Salmonella typhi LPS, whereas the HD-11 macrophage cell line was more responsive to IFN-gamma. These findings are discussed in the context of the genetic differences in SC and TK chickens that may contribute to their divergent disease phenotypes.  相似文献   

4.
Quercetin 3-O-β-(2"-galloyl)-rhamnopyranoside (QGR) is a naturally occurring quercitrin gallate, which is a polyphenolic compound that was originally isolated from Persicaria lapathifolia (Polygonaceae). QGR has been shown to have an inhibitory effect on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. Therefore, this study was conducted to investigate the inhibitory effect of QGR on nitric oxide production and inducible nitric oxide synthases (iNOS) expression in LPS-stimulated Balb/c mice. To accomplish this, 10 mg/kg of QGR was administered via gavage once a day for 3 days. iNOS was then induced by intraperitoneal injection of LPS. Six hours after the LPS treatment the animals were sacrificed under ether anethesia. The serum levels of NO were then measured to determine if QGR exerted an inhibitory effect on NO production in vivo. LPS induced an approximately 6 fold increase in the expression of NO. However, oral administration of QGR reduced the LPS induced increase in NO by half. Furthermore, RT-PCR and western blot analysis revealed that the increased levels of iNOS expression that occurred in response to treatment with LPS were significantly attenuated in response to QGR pretreatment. Histologically, LPS induced the infiltration of polymorphonuclear neutrophils in portal veins and sinusoids and caused the formation of a large number of necrotic cells; however, pretreatment with QGR attenuated these LPS induced effects. Taken together, these results indicate that QGR inhibits iNOS expression in vivo as well as in vitro and has antiinflammatory potentials.  相似文献   

5.
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6.
OBJECTIVE: To determine the amount of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) activity in alveolar macrophages in response to Actinobacillus pleuropneumoniae (APP) by determining nitric oxide (NO) and prostaglandin E2 (PGE2) concentrations. SAMPLE POPULATION: Freshly isolated porcine alveolar macrophages. PROCEDURE: Alveolar macrophages were incubated for 48 hours with APP (1 X 10(4) colony-forming units/mL), interleukin-1beta, (IL-1beta; 5 U/mL), tumor necrosis factor-alpha (TNFalpha; 500 U/mL), interferon-gamma (IFN-gamma, 100 U/mL), or lipopolysaccharide (LPS; 10 microg/mL). In a second experiment, alveolar macrophages were incubated with fresh medium (negative control), APP alone, or APP with 1 of the following: IL-1beta, TNF-alpha, or IFN-gamma. In a third experiment, alveolar macrophages were incubated with fresh medium (negative control), LPS (positive control), APP alone, or APP with 1 of the following: an iNOS inhibitor (3.3 microM), a COX-2 inhibitor (10 microM); or both the iNOS and COX-2 inhibitors. Supernatant was obtained at 0, 3, 6, 9, 12, 24, and 48 hours after treatment for determination of NO and PGE2 production. RESULTS: The addition of APP to alveolar macrophages resulted in significant increases in NO and PGE2 production. The addition of APP and IFN-gamma synergistically induced NO production. Inhibition of iNOS and COX-2 decreased NO and PGE2 production, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro activation of alveolar macrophages by APP results in increased production of NO and PGE2. Nitric oxide and PGE2 production appears to be largely dependent on iNOS and COX-2 activity. Pharmacologic modulation of iNOS and COX-2 activity may represent a therapeutic target for pigs with pleuropneumonia.  相似文献   

7.
Lipopolysaccharide (LPS) is a Gram-negative bacteria cell wall component that activates monocytes and macrophages to produce nitric oxide (NO) from inducible nitric oxide synthase. Nitric oxide production in the plasma of chickens peaks 5–6-h post-i.v. LPS injection reflecting iNOS activation. To determine monocyte responsiveness after an i.v. LPS injection, a time course study was conducted examining the concentrations among peripheral blood leukocytes post-i.v. LPS injection in male and female chickens, the proportions among peripheral mononuclear leukocyte (PBMC; containing lymphocytes, thrombocytes, and monocytes) populations isolated from the blood samples collected at various times post-i.v. LPS treatment, and the ability of monocytes to produce NO with and without further LPS stimulation in vitro using the PBMC NO production assay. Additionally, monocyte extravasation activity was determined by analyzing macrophage proportions after the i.v. LPS injection in spleen, lung, and liver tissues. Blood was collected from male and female chickens at 0 h (pre-LPS injection control) and at 1, 3, 6, 24, and 48 h post-LPS injection, and additionally, at 72 h from female chickens. Tissues were collected 0, 1, 6, and 48 h post-i.v. LPS injection from male chickens. Monocyte concentrations dropped substantially by 1 h in both males and females. In males, monocyte concentrations returned to control concentrations by 6 h and increased at 24- and 48-h post-LPS injection, whereas in females, monocyte concentrations recovered more slowly, returning to near control concentrations by 24–48-h and increasing above control levels by 72 h. Lipopolysaccharide stimulated NO production by PBMC cultures established from blood samples obtained at various times post-LPS injection in vivo followed the same pattern as monocyte concentrations in the blood. Hence, NO concentrations within PBMC cultures were dependent upon the number of monocytes that were in the PBMC cultures isolated at different times post-i.v. LPS injection. Furthermore, macrophage proportions in spleen tissues responded similarly to monocyte concentrations in the blood, decreased in lung tissue, and varied widely in liver tissue throughout 48 h after an LPS injection. Monocytes and other leukocytes may attach to the endothelium post-i.v. LPS injection preventing the monocytes from entering the needle during blood collection resulting in what seems to be leukopenia in blood and in PBMC cultures attenuating NO production in PBMC cultures. Furthermore, monocyte differentiation and recruitment from the bone marrow is a likely contributor to the reconstitution and rise of monocyte concentrations in blood samples post-i.v. LPS injection.  相似文献   

8.
LPS is one of the pathogen associated molecular patterns that activates Toll-like receptor 4 (TLR4) signaling pathway eliciting antiviral host responses in mammals although information on such responses in avian species is scarce. Our objectives were to characterize the LPS induced innate responses particularly the expression of LPS receptors (TLR4, CD14) in avian macrophages and observe whether TLR4 mediated induction of NO can elicit antiviral response against infectious laryngotracheitis virus (ILTV) replication. We found that LPS was capable of inducing the expression of TLR4, CD14 and NO production but not the type 1 interferons in an avian macrophage cell line, MQ-NCSU. We also showed that TLR4 mediated NO production can lead to antiviral response against ILTV replication when MQ-NCSU cells were treated with LPS and the resultant supernatant was then transferred to ILTV replicating cells to assess antiviral activity. Antiviral activity of NO was blocked by a selective inhibitor, S-methylisothiourea sulfhate that inhibits inducible NO synthase. This observation confirms that the antiviral activity is positively correlated with NO production. The data show that LPS can be a potential innate immune stimulant that can be used against ILTV infection in chickens that require further evaluation in vivo.  相似文献   

9.
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10.
Dendritic cells (DC) are important cells at the interface between innate and adaptive immunity. DC have a key role in antigen processing and presentation to T cells. Effector functions of DC related to innate immunity have not been explored extensively. We show that bovine monocyte-derived DC (mDC) express inducible nitric oxide synthase (iNOS) mRNA and protein and produce NO upon triggering with interferon-gamma (IFN-gamma) and heat-killed Listeria monocytogenes (HKLM). An immunocytochemical analysis revealed that a sizeable subset (20-60%) copiously expresses iNOS (iNOShi) upon IFN-gamma/HKLM triggering, whereas the other subset expressed low levels of iNOS (iNOSlo). Monocyte-derived macrophages (mMphi) are more homogeneous with regard to iNOS expression. The number of cells within the iNOSlo mDC subset is considerably larger than the number of dead cells or cells unresponsive to IFN-gamma/HKLM. The large majority of cells translocated p65 to the nucleus upon triggering by IFN-gamma/HKLM. A contamination of mDC with iNOS-expressing mMphi was excluded as follows. (i) Cell surface marker analysis suggested that mDC were relatively homogeneous, and no evidence for a contaminating subset expressing macrophage markers (e.g. high levels of CD14) was obtained. (ii) iNOS expression was stronger in iNOShi mDC than in mMphi. The use of maturation-promoting stimuli revealed only subtle phenotypic differences between immature and mature DC in cattle. Nevertheless, these stimuli promoted development of considerably fewer iNOShi mDC upon triggering with IFN-gamma/HKLM. Immunocytochemical results showed that although a significant proportion of cells expressed iNOS only or TNF only upon triggering with IFN-gamma/HKLM, a significant number of cells expressed both iNOS and TNF, suggesting that TNF and iNOS producing (TIP) DC are present within bovine mDC populations obtained in vitro.  相似文献   

11.
Bighorn sheep are more susceptible to respiratory infection by Mannheimia haemolytica than are domestic sheep. In response to bacterial challenge, macrophages produce a number of molecules that play key roles in the inflammatory response, including highly reactive nitrogen intermediates such as nitric oxide (NO). Supernatants from monocyte-derived macrophages cultured with M. haemolytica LPS were assayed for nitric oxide activity via measurement of the NO metabolite, nitrite. In response to LPS stimulation, bighorn sheep macrophages secreted significantly higher levels of NO compared to levels for non-stimulated macrophages. In contrast, levels of NO produced by domestic sheep macrophages in response to M. haemolytica LPS did not differ from levels detected in non-stimulated cell cultures. Nitrite levels detected in supernatants of LPS-stimulated bighorn macrophage cultures treated with an inducible nitric oxide synthase (INOS) inhibitor, N(G)-monomethyl-L-arginine, were similar to that observed in non-stimulated cultures indicating a role for the iNOS pathway.  相似文献   

12.
The metabolic NO pathway, catalyzed by the enzyme NO synthase in macrophages, is a key defense element against viruses and tumors. However, arginase is an other enzyme able to metabolize the substrate L-arginine, and the two enzymes are alternatively regulated by Th1 and Th2 cytokines in murine macrophages. Marek's disease is characterized by strong immunosuppression and development of T-cell lymphomas in chickens. Inoculation of the very virulent strain of MDV RB-1B induced strong and long-lasting arginase macrophage-dependent activity, which was inhibited by L-norvaline in vitro, but induced low NO production in monocytes and splenocytes from highly susceptible B(13)/B(13) chickens. By contrast, in B(21)/B(21) chickens genetically resistant to tumor development, RB-1B induced a weak and transient increase in arginase activity and strong NO production. The vaccinal HVT strain did not induce any arginase activity in monocytes or splenocytes. Moreover, vaccination with HVT prevented tumor appearance after RB-1B challenge and increase in arginase activity, but favored NO production in susceptible chickens. Differential expression of NO synthase and arginase was modulated in chicken macrophages, with IFN-gamma and LPS being strong inducers of both, depending on the type of macrophage, and TGF-beta 1 and PGE(2) stimulating only arginase activity. This increase in arginase activity in macrophages from chickens inoculated with Marek's disease virus might thus be due to a direct effect of the virus on macrophages, possibly through viral products, or to indirect effects on the cytokine balance.  相似文献   

13.
Macrophages are major effectors against Salmonella infection, and also transport bacteria between host tissues and provide a protected site for intracellular bacterial replication. We hypothesized that differences in chicken macrophage responses to Salmonella enterica serovar Enteritidis (SE) and serovar Typhimurium (ST) played a role in preferential infection of eggs by SE compared with ST. To test this hypothesis, we determined bacterial phagocytosis and intracellular viability and macrophage nitric oxide (NO) production following in vitro infection with SE or ST in the presence or absence of interferon-gamma (IFN-gamma). The effects of bacterial components, lipopolysaccharide (LPS), outer membrane proteins (OMP) and flagella, on NO production were also assessed. Our results showed: (1) in the presence or absence of IFN-gamma, the percentage macrophages phagocytizing SE and ST was similar; (2) the number of intracellular viable SE was significantly reduced compared with ST in the presence or absence of IFN-gamma; (3) increased macrophage necrosis was seen in the presence of IFN-gamma and ST; (4) Salmonella infection acted synergistically with IFN-gamma in induction of nitric oxide production; and (5) in the absence of IFN-gamma, macrophages produced significantly greater NO following treatment with SE outer membrane protein or flagella compared with ST OMP or flagella, while in the presence of IFN-gamma significantly less NO was produced following treatment with SE-LPS compared with ST-LPS. These results suggest that differential responses of chicken macrophages to SE versus ST may result in increased macrophage death with ST, which could result in an increased inflammatory response as compared to SE.  相似文献   

14.
The purpose of this study was to examine iNOS gene expression and activity in macrophages from different chicken genetic lines against various bacterial LPS. Furthermore, the possible involvement of surface LPS receptors as candidates for differential iNOS gene induction in these genetic lines of chicken was also examined. Sephadex-elicited abdominal macrophages (1 x 10(6)) as well as iNOS hyper-responder macrophages from a transformed chicken macrophage cell line, MQ-NCSU, were exposed to 5 microg/ml LPS from E. coli, Shigella flexneri, Serratia marcensces, and Salmonella typhimurium. Nitrite levels were quantitated in the culture supernatant fractions of macrophages after 24h by the Griess method. The results showed that macrophages from K-strain (B(15)B(15)) (range from two separate trials: 31-89 microM) and MQ-NCSU (22-81 microM) were high responders whereas macrophages from both GB1 (B(13)B(13)) (15-38 microM) and GB2 (B(6)B(6)) (7-15 microM) chickens were low responders against all LPSs used. Northern blot analysis revealed that K-strain macrophages expressed higher intensity of 4.5Kb iNOS mRNA (iNOS/beta-actin ratio) than macrophages from GB2 regardless of the LPS source. To elucidate possible molecular mechanism(s) involved in iNOS gene expression in these two strains of chickens, the constitutive expression of LPS-related macrophage cell surface receptors, CD14, Toll-like receptor-2 (TLR2), and Toll-like receptor-4 (TLR4), was examined via flow cytometry using anti-human CD14, TLR2 and TLR4 antibodies. CD14 surface expression and intensity was not different between macrophages from K-strain or GB2 chickens. In contrast, while the overall percentage of TLR4-positive macrophages was the same (K-strain, trial 1=92%, trial 2=62%; GB2, trial 1=91%, trial 2=64%), the mean fluorescence intensity (MFI), an indicator of receptor number, was significantly higher (P=0.05) in K-strain macrophages (MFI: trial 1=145; trial 2=131) than GB2 macrophages (MFI: trial 1=101; trial 2=98). Furthermore, TLR2 (a previously thought candidate as LPS signaling molecule) positive cell numbers were higher in K-strain than the GB2 macrophages in one of the two trials with no difference in the intensity of TLR2 expression in either trial. These findings suggest that the observed differences in iNOS expression and activity among the K-strain (hyper-responder) and GB2 (hypo-responder) chickens are, at least in part, due to differential expression of TLR4 (an LPS signaling molecule), leading to more intense LPS-mediated activation of K-macrophages.  相似文献   

15.
Nitric oxide (NO*) synthesis is induced within many tumors. The time course of NO* synthesis was evaluated during intra-peritoneal Meth A fibrosarcoma progression. While increasing macrophage recruitment into ascites was noted, inducible nitric oxide synthase (iNOS) antigen and function peaked between days 3-6 after tumor implantation. The capacity of cells to respond to LPS and IFNgamma stimulation was markedly depressed on day 9 and 11. Cellular proliferation correlated in an inverse fashion with levels of NO* synthesis. Electron paramagnetic resonance spectroscopy and nitrotyrosine immunostaining failed to show accumulation of characteristic target cell lesions induced by NO*. These findings lead us to conclude that NO* production was increasingly suppressed during Meth A tumor progression. Depression of NO* production did not correlate with levels of the inhibitory cytokines TGFbeta and IL-10, but could be partially overcome by addition of sepiapterin (a tetrahydrobiopterin prodrug). Thus, depletion of essential co-factors necessary for iNOS function may contribute to depressed NO* responses during cancer progression.  相似文献   

16.
Nitric oxide (NO*) synthesis is induced within many tumors. The timecourse of NO* synthesis was evaluated during intraperitoneal Meth A fibrosarcoma progression. While increasing macrophage recruitment into ascites was noted, inducible nitric oxide synthase (iNOS) antigen and function peaked between days 3-6 after tumor implantation. The capacity of cells to respond to LPS and IFNgamma stimulation was markedly depressed on day 9 and 11. Cellular proliferation correlated in an inverse fashion with levels of NO* synthesis. Electron paramagnetic resonance spectroscopy and nitrotyrosine immunostaining failed to show accumulation of characteristic target cell lesions induced by NO*. These findings lead us to conclude that NO* production was increasingly suppressed during Meth A tumor progression. Depression of NO* production did not correlate with levels of the inhibitory cytokines TGFbeta and IL-10, but could be partially overcome by addition of sepiapterin (a tetrahydrobiopterin prodrug). Thus, depletion of essential co-factors necessary for iNOS function may contribute to depressed NO* responses during cancer progression.  相似文献   

17.
The aim of this study was to evaluate the influence of macrophage alternative activation in the intracellular pathogen natural disease resistance phenotype of the host. Macrophage monolayers from resistant (R) (3) or susceptible (S) (3) cattle donors were treated with 10 ng/ml of bovine recombinant IL-4 (rbIL-4), and infected with virulent and avirulent Mycobacterium bovis (MOI 10:1). Bactericidal assays were performed to assess the bacterial phagocytic index and intracellular survival. Total RNA was reverse transcribed and used to analyze the relative changes in gene expression of IL-10, IL-12, IL-18 IL-1β, TNF-α, MCP-1, MCP-2, IL-6, MIP-1, MIP-3, iNOS, ARGII and SLAM by real time PCR. Cell supernatants were collected and nitric oxide and arginase production was assessed. Apoptosis induction was measured by TUNEL. IL-4 treatment increased the phagocytic index in both R and S macrophages; however intracellular survival was augmented mainly in S macrophages. Alternative activation decreased gene expression of pro-inflammatory cytokines, nitric oxide production and DNA fragmentation mainly in R macrophages. On the other hand, arginase production was not different between R and S macrophages. Alternative activation modifies the macrophage response against M. bovis. IL-4 treatment minimized the functional differences that exist between R and S macrophages.  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.
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20.
本试验利用体内试验和体外试验研究壳聚糖(CHI)对泌乳中期奶牛一氧化氮(NO)免疫调节途径的影响。体内试验:按产奶量、泌乳期、胎次和体重相近的原则,将40头泌乳中期荷斯坦奶牛随机分为5个处理,每个处理8个重复,每个重复1头牛。各处理分别在基础饲粮中添加0、500、1000、1500和2000 mg/kg的CHI。试验期60 d,其中1~30 d为前期,31~60 d为后期。试验期间奶牛自由采食和饮水。体外试验:分为2个子试验,每个试验均采用2×2×2三因子设计,即2个脂多糖(LPS)添加水平(0和10μg/mL)×2个壳寡糖(COS)添加水平(0和160μg/mL)×2个抑制剂添加水平(添加和不添加),共8个处理,每个处理6个重复。2个子试验的抑制剂分别是诱导型一氧化氮合酶(iNOS)抑制剂1400W(添加水平1 mmol/L)和核转录因子-κB(NF⁃κB)抑制剂PDTC(添加水平10 mmol/L)。体内试验结果表明:在试验第60天,血清中NO含量随CHI添加水平增加呈极显著的一次线性(P<0.01)或二次曲线(P<0.01)升高效应,iNOS活性呈趋于显著的一次线性(0.05≤P<0.10)或显著的二次曲线(P<0.05)升高效应;外周血单个核细胞(PBMCs)中iNOS和NF⁃κB基因表达量均呈趋于显著的一次线性(0.05≤P<0.10)或显著的二次曲线(P<0.05)升高效应;上述指标在1500 mg/kg添加水平表现为最高。体外试验结果表明:1)当1400W作为抑制剂,COS显著增加iNOS基因表达量(P<0.05);1400W极显著降低NO含量和iNOS活性(P<0.01)。2)当PDTC作为抑制剂,PDTC显著降低NO含量(P<0.05),极显著降低iNOS和NF⁃κB的基因表达量(P<0.01)。3)在脂多糖(LPS)刺激的条件下,NO含量、iNOS活性和iNOS基因表达量均极显著增加(P<0.01),而对NF⁃κB基因表达量无显著影响(P>0.05);而添加COS又能够缓解LPS引起的NO含量、iNOS活性和iNOS基因表达量的升高。上述结果提示,COS可通过增加iNOS和NF⁃κB的基因表达量,升高iNOS的活性,从而增加机体内NO的产生,对奶牛免疫功能起到调节作用,而且这种作用呈现剂量依赖效应。此外,COS引起的PBMCs中NO含量的升高,是通过增加iNOS和NF⁃κB的基因表达量,提高iNOS活性来完成的,且COS对奶牛PBMCs中NO途径的相关指标具有双向调节作用。综上所述,CHI可通过NO分子途径发挥免疫调节功能,且添加水平为1500 mg/kg时效果最佳。  相似文献   

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