Cordycepin is an Immunoregulatory Active Ingredient of Cordyceps sinensis

2008 ◽  
Vol 36 (05) ◽  
pp. 967-980 ◽  
Author(s):  
Xiaoxia Zhou ◽  
Liping Luo ◽  
Waike Dressel ◽  
Gulibahaer Shadier ◽  
Doreen Krumbiegel ◽  
...  
Keyword(s):  
Immune Cells ◽  
Active Ingredient ◽  
Mononuclear Cells ◽  
Binding Activity ◽  
Cordyceps Sinensis ◽  
Chinese Drug ◽  
Dependent Manner ◽  
Tnf Α ◽  
Ifn Γ ◽  
Regulatory Effects

We have reported that cordycepin, an adenosine derivative from the fungus Cordyceps, increased interleukin (IL)-10 expression, decreased IL-2 expression and suppressed T lymphocyte activity. In the present study, we further characterized the regulatory effects of cordycepin on human immune cells. Moreover, a traditional Chinese drug, Cordyceps sinensis (CS) that contains cordycepin, was also investigated. Cytometric Bead Array (CBA) was used to determine the concentrations of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-α and IFN-γ in culture of peripheral blood mononuclear cells (PBMCs). The results showed that both cordycepin and CS up-regulated IL-10, IL-1β, IL-6, IL-8 and TNF-α; at the same time, they suppressed phytohemagglutinin (PHA)-induced production of IL-2, IL-4, IL-5, IFN-γ and IL-12. As compared to cordycepin, CS displayed its regulatory effects on IL-2 and IL-10 in a similar dose-dependent manner even with higher efficiency. The binding activity of transcription factors in a human monocytic cell line THP-1 was tested by the trans-AM method, and a higher binding activity of SP1 and SP3 was observed in cordycepin or CS treated cells compared to the control. These results led to the opinion that cordycepin and CS pleiotropically affected the actions of immune cells and cytokine network in a similar fashion. Cordycepin could be an important immunoregulatory active ingredient in Cordyceps sinensis. In addition, CS may contain substances which possess synergism with cordycepin, as CS showed a higher efficiency in the production of IL-10 and IL-2 than cordycepin. However, merits of these effects in pharmacology and clinical medicine have yet to be proven and the precise mechanism of these immune regulatory actions should be researched.

Activation of Selective Transcription Factors and Cytokines by Water-Soluble Extract from Lentinus lepideus

2003 ◽  
Vol 228 (6) ◽  
pp. 749-758 ◽  
Author(s):  
Mirim Jin ◽  
Hyung Jin Jung ◽  
Jeong June Choi ◽  
Hyang Jeon ◽  
Jin Hwan Oh ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Post Treatment ◽  
Water Soluble ◽  
Dependent Manner ◽  
Soluble Extract ◽  
Transient Transfection Assay ◽  
Gm Csf ◽  
Tnf Α ◽  
Water Soluble Extract

We isolated a water-soluble extract, PG101, from cultured mycelia of Lentinus lepideus. Treatment of human peripheral blood mononuclear cells (PBMCs) with PG101 increased levels of TNF-α, IL-1β, IL-10, and IL-12 by 100- to 1000-fold, whereas GM-CSF and IL-18 were activated by an order of magnitude. On the contrary, IFN-γ and IL-4 were not affected. The response to PG101 occurred in a dose- and time-dependent manner. From the human PBMCs treated with PG101, TNF-α was a first cytokine to be activated, detectable at 2 hr post-treatment followed by IL-1β at 6 hr post-treatment. IL-12 and IL-10 were the next to follow. GM-CSF and IL-18 both showed significant increases 24 hr after treatment. When PBMCs were sorted into various cell types, monocyte/macrophages, but not T and B cells, were the major target cell type responsive to PG101. Consistent with this result, the profile of cytokine expression upon PG101 treatment was comparable between PBMCs and a human promonocytic cell line (U937), whereas cell lines of T cell and myeloid origins did not respond to PG101. Data from a transient transfection assay involving specific reporter plasmids indicated that cellular transcription factor such as NF-κB, but not AP-1, was highly activated by PG101. Results from a gel retardation assay and the experiment involving a specific NF-κB inhibitor confirmed the involvement of NF-κB. Despite its significant biological effect on various cytokines, PG101 remained nontoxic in both rats and PBMCs even at a biological concentration approximately 20 times greater. PG101 demonstrates great potential as a therapeutic immune modulator.

scholarly journals Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease

2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Kawaljit Kaur ◽  
Shahram Vaziri ◽  
Marcela Romero-Reyes ◽  
Avina Paranjpe ◽  
Anahid Jewett
Keyword(s):  
Periodontal Disease ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Oral Disease ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Ifn Γ ◽  
And Function

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of peripheral blood.

scholarly journals Effect of Steroids on Lipopolysaccharide/Interleukin 2-Induced Interleukin 18 Production in Peripheral Blood Mononuclear Cells

2002 ◽  
Vol 30 (2) ◽  
pp. 144-160 ◽  
Author(s):  
M Kodama ◽  
HK Takahashi ◽  
H Iwagaki ◽  
H Itoh ◽  
T Morichika ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Steroid Treatment ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Enhanced Production ◽  
Blood Mononuclear Cells ◽  
Ifn Γ ◽  
Cytokine Cascade

Interleukin (IL) 18, a powerful inducer of the immunoregulatory cytokine interferon-γ (IFN-γ), presents upstream of the cytokine activation cascade in the inflammatory response. The anti-inflammatory properties of steroids permit their use in various conditions, although effects are transient and pathological states are not fully relieved by short-term steroidal use. We examined the effect of lipopolysaccharide (LPS)/IL-2 on the cytokine cascade in human peripheral blood mononuclear cells (PBMCs). We also examined the effect of steroids on LPS/IL-2-induced cytokine production in human PBMCs taken from healthy volunteers. Cell-free supernatant fractions were assayed for IL-18, IL-12, IL-2, IFN-γ and IL-10 protein, using enzyme-linked immunosorbent assays, and synergy between LPS and IL-2 in enhanced production of IL-18 was observed. Steroids suppressed the production of IL-18 and other secondary cytokines in LPS/IL-2-stimulated PBMCs, in a concentration- and time-dependent manner, although inhibition was incomplete even at high concentrations. Effects of steroid treatment on expression of membrane-bound LPS receptor antigen (mCD14) and intercellular adhesion molecule-1 (ICAM-1) in PBMCs were studied by flow cytometric analysis. Steroid treatment up-regulated mCD14 expression in a concentration-dependent manner, with no effect on ICAM-1 expression. These results suggest that the incomplete counteraction of steroids in the LPS/IL-2-initiating cytokine cascade is due, at least partly, to the up-regulation of mCD14 by steroid preparations, which increases susceptibility to bacterial endotoxins.

Candida tropicalis induces pro-inflammatory cytokine production, NF-κB and MAPKs pathways regulation, and dectin-1 activation

2018 ◽  
Vol 64 (12) ◽  
pp. 937-944 ◽  
Author(s):  
Zhimin Duan ◽  
Qing Chen ◽  
Rong Zeng ◽  
Leilei Du ◽  
Caixia Liu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Inflammatory Cytokine ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Downstream Signaling ◽  
Tnf Α ◽  
Mitogen Activated Protein

The prevalence of Candida infection induced by non-albicans Candida (NAC) species is increasing. However, as a common NAC species, C. tropicalis has received much less study in terms of host immunity than C. albicans has. In this study, we evaluated the pro-inflammatory cytokine responses evoked by C. tropicalis and determined whether dectin-1 and downstream NF-κB and mitogen-activated protein kinases (MAPKs) signaling pathways played roles in inflammation in human peripheral blood mononuclear cells (PBMCs) and THP-1 macrophage-like cells. Exposure of PBMCs and THP-1 macrophage-like cells to C. tropicalis led to the enhanced gene expression and secretion of TNF-α and IL-6 in a time- and dose-dependent manner. THP-1 macrophage-like cells being challenged by C. tropicalis resulted in the activation of the NF-κB, p38, and ERK1/2 MAPK signaling pathways. We also found that the expression of dectin-1 was increased with C. tropicalis treatment. These data reveal that dectin-1 may play a role in sensing the inflammation response induced by C. tropicalis and that NF-κB and MAPK are involved in the downstream signaling pathways in macrophages.

scholarly journals The Effects of Oral Liposomal Glutathione and In Vitro Everolimus in Altering the Immune Responses against Mycobacterium bovis BCG Strain in Individuals with Type 2 Diabetes

2021 ◽  
Vol 12 (1) ◽  
pp. 16-26
Author(s):  
Kimberly To ◽  
Ruoqiong Cao ◽  
Aram Yegiazaryan ◽  
James Owens ◽  
Kayvan Sasaninia ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Immune Cells ◽  
Mycobacterial Infection ◽  
Drug Resistant ◽  
Tnf Α ◽  
Resistant Strains ◽  
Ifn Γ ◽  
Drug Resistant Strains

Abstract Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) still remains a devastating infectious disease in the world. There has been a daunting increase in the incidence of Type 2 Diabetes Mellitus (T2DM) worldwide. T2DM patients are three times more vulnerable to M. tb infection compared to healthy individuals. TB-T2DM coincidence is a challenge for global health control. Despite some progress in the research, M. tb still has unexplored characteristics in successfully evading host defenses. The lengthy duration of treatment, the emergence of multi-drug-resistant strains and extensive-drug-resistant strains of M. tb have made TB treatment very challenging. Previously, we have tested the antimycobacterial effects of everolimus within in vitro granulomas generated from immune cells derived from peripheral blood of healthy subjects. However, the effectiveness of everolimus treatment against mycobacterial infection in individuals with T2DM is unknown. Furthermore, the effectiveness of the combination of in vivo glutathione (GSH) supplementation in individuals with T2DM along with in vitro treatment of isolated immune cells with everolimus against mycobacterial infection has never been tested. Therefore, we postulated that liposomal glutathione (L-GSH) and everolimus would offer great hope for developing adjunctive therapy for mycobacterial infection. L-GSH or placebo was administered to T2DM individuals orally for three months. Study subjects’ blood was drawn pre- and post-L-GSH/or placebo supplementation, where Peripheral Blood Mononuclear Cells (PBMCs) were isolated from whole blood to conduct in vitro studies with everolimus. We found that in vitro treatment with everolimus, an mTOR (membrane target of rapamycin) inhibitor, significantly reduced intracellular M. bovis BCG infection alone and in conjunction with L-GSH supplementation. Furthermore, we found L-GSH supplementation coupled with in vitro everolimus treatment produced a greater effect in inhibiting the growth of intracellular Mycobacterium bovis BCG, than with the everolimus treatment alone. We also demonstrated the functions of L-GSH along with in vitro everolimus treatment in modulating the levels of cytokines such as IFN-γ, TNF-α, and IL-2 and IL-6, in favor of improving control of the mycobacterial infection. In summary, in vitro everolimus-treatment alone and in combination with oral L-GSH supplementation for three months in individuals with T2DM, was able to increase the levels of T-helper type 1 (Th1) cytokines IFN-γ, TNF-α, and IL-2 as well as enhance the abilities of granulomas from individuals with T2DM to improve control of a mycobacterial infection.

scholarly journals Meta-Analysis: Randomized Trials of Lactobacillus plantarum on Immune Regulation Over the Last Decades

2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Zhao ◽  
Chuantao Peng ◽  
Hafiz Arbab Sakandar ◽  
Lai-Yu Kwok ◽  
Wenyi Zhang
Keyword(s):  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Central Register ◽  
Tnf Α ◽  
Ifn Γ ◽  
The Mean ◽  
Regulatory Effects ◽  
Mean Differences ◽  
Necrosis Factor

Lactobacillus (L.) plantarum strains, belong to lactic acid bacteria group, are considered indispensable probiotics. Here, we performed meta-analysis to evaluate the regulatory effects of L. plantarum on the immunity during clinical trials. This meta-analysis was conducted by searching across four most common literature databases, namely, Cochrane Central Register of Controlled Trials, Web of Science, Embase, and PubMed. Clinical trial articles that met the inclusion and exclusion criteria were analyzed by Review Manager (version 5.3). p-value < 0.05 of the total effect was considered statistically significant. Finally, total of 677 references were retrieved, among which six references and 18 randomized controlled trials were included in the meta-analysis. The mean differences observed at 95% confidence interval: interleukin (IL)-4, −0.48 pg/mL (−0.79 to −0.17; p < 0.05); IL-10, 9.88 pg/mL (6.52 to 13.2; p < 0.05); tumor necrosis factor (TNF)-α, −2.34 pg/mL (−3.5 to −1.19; p < 0.05); interferon (IFN)-γ, −0.99 pg/mL (−1.56 to −0.41; p < 0.05). Therefore, meta-analysis results suggested that L. plantarum could promote host immunity by regulating pro-inflammatory and anti-inflammatory cytokines.

scholarly journals Protective effect of Cordyceps sinensis extract on lipopolysaccharide-induced acute lung injury in mice

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Shuiqiao Fu ◽  
Weina Lu ◽  
Wenqiao Yu ◽  
Jun Hu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Weight Ratio ◽  
Cordyceps Sinensis ◽  
Myeloperoxidase Activity ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Tnf Α ◽  
Cox 2

Abstract Background: To study the protective effect of Cordyceps sinensis extract (Dong Chong Xia Cao in Chinese [DCXC]) on experimental acute lung injury (ALI) mice. Methods and results: ALI model was induced by intratracheal-instilled lipopolysaccharide (LPS, 2.4 mg/kg) in BALB/c male mice. The mice were administrated DCXC (ig, 10, 30, 60 mg/kg) in 4 and 8 h after receiving LPS. Histopathological section, wet/dry lung weight ratio and myeloperoxidase activity were detected. Bronchoalveolar lavage fluid (BALF) was collected for cell count, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and nitric oxide (NO) in BALF was detected by ELISA, the protein and mRNA expression of nuclear factor-κB p65 (NF-κB p65), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung tissue was detected by Western blot and RT-PCR. The result showed that DCXC could reduce the degree of histopathological injury, wet/dry weight ratio (W/D ratio) and myeloperoxidase activity (P<0.05) with a dose-dependent manner. The increased number of total cells, neutrophils and macrophages in BALF were significantly inhibited by DCXC treatment (P<0.05). The increased levels of TNF-α, IL-1β, IL-6 and NO in BALF after LPS administration was significantly reduced by DCXC (P<0.05). In addition, the increased protein and mRNA levels of iNOS, COX-2 and NF-κB p65 DNA binding ability in LPS group were dose-dependently reduced by DCXC treatment (P<0.05). Conclusion: DCXC could play an anti-inflammatory and antioxidant effect on LPS-induced ALI through inhibiting NF-κB p65 phosphorylation, and the expression of COX-2 and iNOS in lung. The result showed that DCXC has a potential protective effect on the ALI.

scholarly journals Streptococcus pneumoniae Autolysis Prevents Phagocytosis and Production of Phagocyte-Activating Cytokines

2009 ◽  
Vol 77 (9) ◽  
pp. 3826-3837 ◽  
Author(s):  
Anna Martner ◽  
Susann Skovbjerg ◽  
James C. Paton ◽  
Agnes E. Wold
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 12 ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Exact Function ◽  
Ifn Γ ◽  
Dose Dependent

ABSTRACT Streptococcus pneumoniae is a major pathogen in humans. The pathogenicity of this organism is related to its many virulence factors, the most important of which is the thick pneumococcal capsule that minimizes phagocytosis. Another virulence-associated trait is the tendency of this bacterium to undergo autolysis in stationary phase through activation of the cell wall-bound amidase LytA, which breaks down peptidoglycan. The exact function of autolysis in pneumococcal pathogenesis is, however, unclear. Here, we show the selective and specific inefficiency of wild-type S. pneumoniae for inducing production of phagocyte-activating cytokines in human peripheral blood mononuclear cells (PBMC). Indeed, clinical pneumococcal strains induced production of 30-fold less tumor necrosis factor (TNF), 15-fold less gamma interferon (IFN-γ), and only negligible amounts of interleukin-12 (IL-12) compared with other closely related Streptococcus species, whereas the levels of induction of IL-6, IL-8, and IL-10 production were similar. If pneumococcal LytA was inactivated by mutation or by culture in a medium containing excess choline, the pneumococci induced production of significantly more TNF, IFN-γ, and IL-12 in PBMC, whereas the production of IL-6, IL-8, and IL-10 was unaffected. Further, adding autolyzed pneumococci to intact bacteria inhibited production of TNF, IFN-γ, and IL-12 in a dose-dependent manner but did not inhibit production of IL-6, IL-8, and IL-10 in response to the intact bacteria. Fragments from autolyzed bacteria inhibited phagocytosis of intact bacteria and reduced the in vitro elimination of pneumococci from human blood. Our results suggest that fragments generated by autolysis of bacteria with reduced viability interfere with phagocyte-mediated elimination of live pneumococci.

Intracellular Cytokine Profile of Cord and Adult Blood Lymphocytes

Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 11-18 ◽  
Author(s):  
I.M.H. Chalmers ◽  
G. Janossy ◽  
M. Contreras ◽  
C. Navarrete
Keyword(s):  
Flow Cytometry ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Peripheral Blood Lymphocytes ◽  
Cytokine Profile ◽  
Color Flow ◽  
Blood Lymphocytes ◽  
Tnf Α ◽  
Ifn Γ

Umbilical cord blood (CB) transplantation is thought to be associated with a reduced risk of severe graft-versus-host-disease (GVHD) compared with bone marrow transplantation (BMT). The cytokine cascade is known to be important in the pathogenesis of GVHD; however, previous studies investigating the cytokine secretion pattern of CB cells have been contradictory because of variations in experimental techniques. In this study, the cytokine profile of cord and adult blood lymphocytes and lymphocyte subsets has been assessed at the single-cell level by flow cytometry, using CD4/CD8 and CD45RA/CD45RO markers. Cord and adult blood mononuclear cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin in the presence of monensin. After 4 to 24 hours of incubation, interleukin-2 (IL-2), IL-4, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) production was measured by three-color flow cytometry. The results show that cord blood lymphocytes (CBL) produce less IL-2, IL-4, IFN-γ, and TNF-α than adult peripheral blood lymphocytes (ABL). Further subset analysis showed that in CBL the majority of cytokine producing cells were CD4+CD45RA+, whereas in ABL the cytokine-producing cells were both CD4+CD45RO+ and CD8+CD45RO+. These results suggest that the reduced incidence of GVHD in CB transplantation may partly due to the altered cytokine profile seen in CBL.

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