scholarly journals Macrophage immunomodulatory activity of Acanthopanax senticousus polysaccharide nanoemulsion via activation of P65/JNK/ikkαsignaling pathway and regulation of Th1/Th2 Cytokines

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12575
Author(s):  
Xianghui Li ◽  
Zhiqiang Zhang ◽  
Zhenhuan Guo ◽  
Li Zhao ◽  
Yonglu Liu ◽  
...  

Nanoemulsions (NE) are used widely in pharmaceutical drug formulations and vaccine preparation, and Acanthopanax senticousus polysaccharide (ASPS) is a natural bioactive compound with immunostimulatory activity. Therefore, NE-loaded ASPS is expected to provide immunological enhancement for effective treatment. In the present study, Acanthopanax senticousus polysaccharide (ASPS was encapsulated into nanoemulsions, the resultant ASPS–NE were coated with a negative charge, and the immune enhancement mechanism of these ASPS-NE formulations was analyzed. The immunosuppressive animal models (70 ICR mice, male) for the study were established using cyclophosphamide. In addition, the activation of splenocyte proliferation, phagocytosis of the macrophages, the ratio of CD4+ to CD8+, the concentrations of the cytokines in serum, Western blot analysis was used for the analysis of the P65/JNK/ikk α signaling pathway in the peritoneal macrophage s. The results revealed that the ASPS-NE could stimulated the proliferation of splenocytes and enhance immunity. The ASPS-NE induced the expression of different cytokines (TNF-α, IFN-γ, IL-2, and IL-6), could activate the expressions of P65, JNK, and ikkα, and regulated the Th1/Th2 cytokines. These findings demonstrated the potential of ASPS-NE formulations for drug delivery and to induce potent and sustained immune responses.

2018 ◽  
Vol 57 (6) ◽  
pp. 757-763 ◽  
Author(s):  
C Pagliari ◽  
L Kanashiro-Galo ◽  
A C C Jesus ◽  
M G Saldanha ◽  
M N Sotto

AbstractMucosal lesions of paracoccidioidomycosis (PCM) are frequently described and clinically important. Macrophages are classified as M1 or M2. M1 are proinflammatory and M2 are related to chronicity. Dectin-1 recognizes β-glucan and plays an important role against fungal cells. The objective was to verify the presence of M1, M2, and dectin-1 and a possible correlation with Th1/Th2 cytokines in mucosal PCM lesions. In sum, 33 biopsies of oral PCM were submitted to histological and immunohistochemistry analysis, and positive cells were quantified. Eleven biopsies were characterized by compact granulomas (G1), 12 with loose granulomas (G2), and 10 with both kind of granulomas (G3). pSTAT-1 was equally increased in the three groups. G1 was characterized by an increased number of CD163+ macrophages. G2 presented similar number of arginase 1, iNOS, and CD163 expressing cells. G3 presented an increased number of cells expressing arginase 1 and CD163 over iNOS. G1 and G3 presented high number of cells expressing interferon (IFN)-γ; interleukin (IL) 5 was increased in G2 and G3; the expression of IL10 was similar among the three groups, and the expression of tumor necrosis factor (TNF)-α was higher in G3. G1 correlates to Th1 cytokines and pSTAT-1 and G2 correlates to Th2 cytokines. G3 presents both kinds of cytokines. We could not associate the expression of arginase-1, CD163, iNOS, and dectin-1 with the pattern of cytokines or kind of granuloma.


2020 ◽  
Author(s):  
Daimon P. Simmons ◽  
Hung N. Nguyen ◽  
Emma Gomez-Rivas ◽  
Yunju Jeong ◽  
Antonia F. Chen ◽  
...  

AbstractMacrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a super-activated macrophage state in rheumatoid arthritis. We implicated IFN-γ as a key regulator of SLAMF7 expression. Engaging this receptor drove an exuberant wave of inflammatory cytokine expression, and induction of TNF-α following SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients, but in gut macrophages from active Crohn’s disease patients and lung macrophages from severe COVID-19 patients. This suggests a central role for SLAMF7 in macrophage super-activation with broad implications in pathology.


2020 ◽  
Vol 8 (8) ◽  
pp. 1175
Author(s):  
Sun Woo Jin ◽  
Gi Ho Lee ◽  
Min Jung Jang ◽  
Gyeong Eun Hong ◽  
Jae Young Kim ◽  
...  

Recently, Lactococcus lactis subsp. lactis has been reported to have immunostimulating properties in an immunosuppressed-animal model. However, the immunological activities of Lactococcus lactis and the molecular mechanisms remain unclear. In this report, we evaluated the immunostimulating activity and associated mechanisms of Lactococcus lactis subsp. lactis GCWB1176 (GCWB1176) in macrophages and cyclophosphamide (CTX)-induced immunosuppressed mice. In a series of safety tests, GCWB1176 was found to have a negative response to hemolysis, as well as susceptibility to antibiotics. Administration of GCWB1176 elevated natural killer (NK) cell activities; concanavalin A-induced T cell proliferation; and serum levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-10 and IL-12 in CTX-induced immunosuppressed mice. In RAW264.7 macrophages, treatment with GCWB1176 induced phagocytic activity and increased the production of nitric oxide (NO) and expression of inducible NO synthase. Simultaneously, GCWB1176 increased the production of TNF-α, IFN-γ, IL-1β, IL-10 and IL-12 from mouse splenocytes and RAW264.7 cells. In addition, GCWB1176 significantly increased the transcriptional activities of NF-κB and iNOS. Taken together, GCWB1176 improved immune function through the activation of macrophages and NK cells. These findings suggest that dietary supplementation of GCWB1176 may be used to enhance immunity.


2012 ◽  
Vol 393 (1-2) ◽  
pp. 101-106 ◽  
Author(s):  
Vijaya Lakshmi Simhadri ◽  
Hinrich P. Hansen ◽  
Venkateswara R. Simhadri ◽  
Katrin S. Reiners ◽  
Martina Bessler ◽  
...  

Abstract The interplay between dendritic cells (DCs) and natural killer (NK) cells directs adaptive immune responses. The molecular basis of the cross-talk is largely undefined. Here, we provide evidence for a contribution of CD30 (TNFRSF8) and its ligand CD30L (TNFSF8) expressed on NK cells and DCs, respectively. We demonstrate that CD30-mediated engagement of CD30L induced cytokine secretion from immature DCs via the mitogen-activated protein kinase pathway. Moreover, CD30L engagement promoted differentiation to mature DCs. On the contrary, the engagement of CD30 on NK cells resulted in an NF-κB-dependent release of TNF-α/IFN-γ. These data uncover a novel and unexpected role for CD30/CD30L that contributes to proinflammatory immune responses.


2008 ◽  
Vol 82 (10) ◽  
pp. 4844-4852 ◽  
Author(s):  
Jinyan Liu ◽  
Bonnie A. Ewald ◽  
Diana M. Lynch ◽  
Matthew Denholtz ◽  
Peter Abbink ◽  
...  

ABSTRACT Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for human immunodeficiency virus type 1 (HIV-1) and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent preexisting anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily gamma interferon-positive (IFN-γ+) and IFN-γ+/tumor necrosis factor alpha+ (TNF-α+) T-lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of interleukin-2+ (IL-2+) and polyfunctional IFN-γ+/TNF-α+/IL-2+ T-lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited T-lymphocyte responses that were phenotypically distinct from those elicited by rAd5 vectors and suggest the functional relevance of polyfunctional CD8+ and CD4+ T-lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.


2013 ◽  
Vol 10 (3) ◽  
pp. 30-34
Author(s):  
A P Toptygina ◽  
V A Alioshkin

Background. The aim of the study was to investigate peculiarities of immune responses on the vaccination with Priorix in healthy children and patients with atopic dermatitis. Methods. Thirty five healthy children aged 1-2 years old (Group 1) and 15 children the same age with atopic dermatitis (Group 2) were vaccinated with Priorix. Serum level of IgE was measured by ELISA, and serum concentrations of 7 cytokines: IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, and TNF-α were measured by BioPlex technology before vaccination, 7 days, and 30 days after. Serum level of IgE was measured by ELISA. Results. The level of serum IgE relatively decreased or increased on seventh day after vaccination. In a month IgE level returned back. It was found that in group1 51,4% children demonstrated Th1 type response and 48,6% children showed Th2 type response on the vaccination. Similar distribution was obtained in group 2 (53,3% children showed Th1 type response and 46,7% children demonstrated Th2 type). A significant positive correlation was observed between IgE level increasing and Th2 type of immune response. It was shown that 68,6% of children of group 1 and 66,7% of children of group 2 demonstrated after vaccination the superiority of anti-inflammatory IL-10 over pro-inflammatory TNF-α. We suppose that children with atopic dermatitis can be vaccinated with Priorix.


Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5733
Author(s):  
Feng Liu ◽  
Lijia Zhang ◽  
Xi Feng ◽  
Salam A. Ibrahim ◽  
Wen Huang ◽  
...  

The effects of immunomodulatory activity of two types of carboxymethyl pachymaran (CMP-1 and CMP-2) on cyclophosphamide (CTX)-induced mice were investigated. Both CMP-1 and CMP-2 were found to restore the splenomegaly and alleviate the spleen lesions and the mRNA expressions of TLR4, MyD88, p65 and NF-κB in spleen were also increased. CMP-1 and CMP-2 could enhance the immunity by increasing the levels of TNF-α, IL-2, IL-6, IFN-γ, Ig-A and Ig-G in serum. In addition, CMP-1 could increase the relative abundance of Bacteroidetes and reduce the relative richness of Firmicutes at the phylum level. CMP-1 and CMP-2 could reduce the relative abundance Erysipelatoclostridum at the genus level. CMP-1 and CMP-2 might enhance the immune function of immunosuppression mice by regulating the gene expression in the TLR4/NF-κB signaling pathway and changing the composition and abundance of the intestinal microbiota. The results suggested that CMP-1 and CMP-2 would be as potential immunomodulatory agents in functional foods.


Author(s):  
Adryan Fristiohady ◽  
Jumadil ◽  
Wahyuni ◽  
Muh. Hajrul Malaka ◽  
Wa Ode Harnita ◽  
...  

Xestospongia sp. is one of marine sponge belongs to demosponges class that mainly found in Southeast Sulawesi and the secondary metabolites contained in Xestospongia sp. suspected to have immunomodulatory activity. A previous study exhibited the immunomodulatory of Xestospongia sp. ethanolic extract (XEE) at dose of 300 and 400 mg/Kg BW by affecting the phagocytic activity of macrophages. Thus, this study aims to investigate the effect of XEE towards interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) at dose of 300 and 400 mg/Kg BW. Wistar male rats are divided into 4 groups (n=6) randomly and treated for 7 days orally each as follow: group I (XEE dose of 300 mg/KgBW); group II (XEE dose of 400 mg/KgBW); group III (0.5% NaCMC); and group IV (commercial phylantii extract). On day 8, animals were infected with Staphylococcus aureus and left for 1 hour. Animals were sacrificed and the blood was drawn by cardiac puncture (3 mL), followed by analyzed under ELISA Kit for IFN-γ and TNF-α. Collected data were analyzed statistically using SPSS®. The IFN-γ levels obtained were 350.113; 392.970; 118.416; and 61.958 ρg/mL, respectively and the TNF-α were 2808; 1308; 778; and 845.5 ρg/mL, respectively. According to results obtained, both doses of XEE are affecting the IFN-γ and TNF-α levels (p<0.05) compared to group III as negative control, and group IV as positive control. As conclusion, XEE of both doses is increasing IFN-γ and TNF-α levels of animals that respond to phagocytic activity


Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1040
Author(s):  
Erika S. Guimarães ◽  
Jéssica M. Martins ◽  
Marco Túlio R. Gomes ◽  
Daiane M. Cerqueira ◽  
Sergio C. Oliveira

Interleukin-6 (IL-6) is a pleiotropic cytokine promptly produced in response to infections, which contributes to host defense through the stimulation of acute phase immune responses. Brucella abortus is an intracellular bacterium that causes chronic disease in humans and domestic animals and triggers a robust immune response, characterized by the production of inflammatory cytokines. However, the mechanisms of IL-6-related immune responses in the context of Brucella infections are not completely understood. In this report, we describe an increased susceptibility of IL-6 knockout (KO) mice in the early phase of Brucella infection. Furthermore, we demonstrate that IL-6 is required for interferon (IFN)-γ and tumor necrosis factor (TNF)-α induction by infected splenocytes, indicating a protective role for IL-6 against B. abortus that parallels with Th1 type of immune response. Additionally, IL-6 KO mice exhibited reduced splenomegaly during the early phase of the infection. Corroborating this result, IL-6 KO mice displayed reduced numbers of macrophages, dendritic cells, and neutrophils in the spleen and reduced myeloperoxidase activity in the liver compared to wild-type infected mice. However, we demonstrate that IL-6 is not involved in B. abortus intracellular restriction in mouse macrophages. Taken together, our findings demonstrate that IL-6 contributes to host resistance during the early phase of B. abortus infection in vivo, and suggest that its protective role maybe partially mediated by proinflammatory immune responses and immune cell recruitment.


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