scholarly journals Anti-inflammatory effects of a methanol extract of Dictamnus dasycarpus Turcz. root bark on imiquimod-induced psoriasis

Author(s):  
Minjee Choi ◽  
Jun Koo Yi ◽  
Si-Yong Kim ◽  
Jung Hyun Ryu ◽  
Jinhee Lee ◽  
...  

Abstract Background The root bark of Dictamnus dasycarpus Turcz. has been successfully used for the treatment of inflammatory skin conditions such as eczema and pruritus. However, the anti-psoriatic effect of this plant has not until now been investigated. Methods The aim of this project was to investigate whether a methanol extract of Dictamnus dasycarpus Turcz. root bark (MEDD) can be used as a therapeutic agent for psoriasis in C57BL/6 mice model of imiquimod (IMQ)-induced psoriasis. IMQ and MEDD was applied to mouse skin continuously for 7 days. The skin phenotype and the levels of inflammatory cytokines, such as interferon (IFN)-γ and interleukin (IL)-17, were analyzed. The immune cell population was determined by flow cytometry, and STAT1 and 3 protein levels were measured. Results An alleviation of scaly skin phenotype, immune cell infiltration in the dermis, and epidermal hyperplasia was observed after daily MEDD treatment in the lesion-affected area. It was also found that MEDD reduced IL-17 cytokine levels decreased by 44.37% (p < 0.05), the number of IL-17-producing Th17 cells and γδT cells, and the size of the Th1 population secreting IFN-γ decreased by 45.98, 62.21, and 44.42%, respectively (p < 0.05), compared with the vehicle control group. STAT3 signals, associated with IL-17 are also reduced by MEDD. Conclusions An anti-psoriatic effect of MEDD was observed, as determined by decreased skin inflammation, reduced number of inflammatory cytokines, and a smaller population of inflammatory cells. These results contribute to the validation of the use of MEDD in the treatment of psoriasis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1727-1727
Author(s):  
Manuel Schmidt ◽  
Javier de Cristobal ◽  
Astrid Sander ◽  
Bernadette Brzezicha ◽  
Sven A. König Merediz ◽  
...  

Abstract Cytosine-guanine (CpG) motifs containing oligonucleotides (ODN) are commonly used for immunomodulatory purpose in cancer therapy and for the treatment of allergic diseases since they resemble bacterial DNA and serve as “danger signals”. These CpG-ODNs promote predominately a TH1-response with secretion of IL-12 and IFN-γ, In addition their broad potential includes activation of B-cell proliferation, monocyte stimulation and secretion of IgM and IL-6, and stimulation of plasmacytoid DC to produce IFN-α/-β and thus γδT-cells and NK-cells to express CD69 and secrete IFN-γ. Usually phosphorothioate (PS) modifications are to enhance the stability, but these are leading to several side-effects, like severe organ enlargements, morphological changes and immunosuppression in mice. We designed immunomodulatory molecules based on short covalently-closed dumbbell-like structures (dSLIM) to stabilize the DNA without the otherwise necessary PS-modification. To evaluate the anti-tumor effect of the dSLIM molecules we developed an in vitro anti-tumor assay. This assay uses supernatant from dSLIM-activated human PBMCs for incubation with tumor cells in vitro. We observed increased apoptosis and necrosis of the HT-29 tumor cell line after incubation with supernatant from dSLIM-treated PBMC which was significantly higher than the effect of supernatant from non-treated PBMC. In addition, supernatant from dSLIM-treated PBMC increased the expression of HLA-ABC on the tumor cells, a pre-requisite for tumor cell recognition by the immune system. These effects were confirmed with human HEK293 and murine Renca cell lines. Analyzing the effect with neutralizing antibodies to various apoptosis-related cytokines, we observed a crucial role of IFN-γ but not IFN-α or TNFα. To investigate the anti-tumor effects of dSLIM in vivo, we employed a SKH1 murine model which is prone to spontaneous development of papillomas. Using chemicals for initiation and weekly promotion of de novo papilloma development we compared groups of weekly s.c. or i.p. dSLIM injections, respectively, with the PBS control group. The number of papilloma developing mice was significantly lower in the dSLIM groups and the total number of papillomas on all mice was reduced by approximately 50%. In conclusion, we showed that dSLIM immunomodulators exhibit potent anti-tumor effects in vitro and in vivo.


2019 ◽  
Vol 65 (5) ◽  
pp. 432-436
Author(s):  
A.M. Krasnyi ◽  
A.A. Sadekova ◽  
T.G. Sefihanov ◽  
V.V. Vtorushina ◽  
E.G. Krechetova ◽  
...  

Concentrations of eight different cytokines and the level of expression of CD86 and CD163 macrophages were studied in peritoneal fluid in women with endometriosis. It was found that the concentration of both inflammatory (IL-6, IL-8, TNF-α) and anti-inflammatory cytokines (IL-4) as well as the level of macrophage expression of the proinflammatory marker CD86 and anti-inflammatory marker CD163 increased in women with mild external genital endometriosis (1-2 stage), and did not differ from the control group in women with severe endometriosis (3-4 stage). The content of IL-2, IL-10, CM-CSF and IFN-γ in the peritoneal fluid of women with endometriosis did not differ significantly from the control group. The results of the study indicate that the development of external genital endometriosis may be based on insufficient both inflammatory and anti-inflammatory activity of macrophages in the peritoneal fluid.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5412-5412
Author(s):  
Xinzhen Cai ◽  
Jun Ni ◽  
Wei Wu ◽  
Qingqing Shi ◽  
Zou Li ◽  
...  

Abstract Introduction To preliminary study the repair effect of umbilical cordmesenchymal stem cells (UC-MSCs) homing on local and systemic inflammatory microenvironment and immune inflammatory thrombophilia states of the CIA rata by observing the distribution of the UC-MSCs in the CIA rate and the influence of the UC-MSCs on the expression of the inflammatory cytokines IL-10, TNF-α IL-6, IFN-γ and the thrombosis indicators TF, VWF, DD, FIB's. Methods The clean grade, female, 5-week-old SD rats were randomly divided into a control (C) group, model (M) group, UC-MSCs treatment (SU) group, adding AMD3100 to labled UC-MSCs therapy (ASU) group. Except for control group, the other rats were induced as CIA rats model. Treatment group were injected UC-MSCs suspension by tail vein. The rats were sacrificed in the first, the third and the fifth week after transplantation. HE staining was used to observe the pathological changes of joint tissues. The distribution of UC-MSCs in the joint tissue was detected by FISH. ELISA assay was used to observe the expression of inflammation and thrombosis indicators in peripheral blood. The expression of inflammatory factors in the joint tissue were detected by western blot. Results: 1. One week after injection, the expression of SDF-1 in the injuried joint of the group SU was significantly increased compared with the control group, at the same time, the large number of UC-MSCs occured in injured sites. While, adding AMD3100 to labled UC-MSCs were not expressed in the joint tissue. The expression of SDF-1 in the labled UC-MSCs treating group decreased over time, and the number of UC-MSCs reduced in the inflammatory joints. 2. After given UC-MSCs treatment, the levels of pro-inflammatory cytokines IL-6, TNF-α, IFN-γ in the knee and serum were conspicuously reduced compared with the group M since the first week. While the level of anti-inflammatory cytokine IL-10 was increased (p <0.05). After adding AMD3100, the expression of above indicators in the group ASU showed no significant difference compared to the group C. 3. After given UC-MSCs treatment, the levels of TF in serum and DD, FIB, VWF in plasma were conspicuously reduced compared to the group M since the first week (p <0.05). The expression of the above indicators in the group ASU showed no significant difference compared to the group C. Conclusion: 1. UC-MSCs homing to the injured joint tissue is influnced by the local inflammation environment, which is an important way to play its role of immune regulation to improve the immune inflammatory thrombophilia state in CIA rsts. 2. SDF-1/CXCR4 axis is important to the UC-MSCs homing, the antagonist AMD3100 can suppress the UC-MSC homing to the injured site. Funded by Jiangsu Provincial Special Program of Medical Science (BL2012005) Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 19 ◽  
pp. 153303382095180
Author(s):  
Jian Chen ◽  
Xincai Li ◽  
ChaoLin Huang ◽  
Ying Lin ◽  
Qingfu Dai

Objective: This study aimed to investigate the serum inflammatory cytokines levels in patients with COPD, pneumonia and lung cancer, and assess the correlation between the levels of inflammatory cytokines levels and development of these diseases. Methods: Two hundred thirty-two patients including 114 patients with pneumonia, 76 patients with chronic obstructive pulmonary disease (COPD) and 42 patients with lung cancer, and 62 age-matched healthy volunteers as controls were enrolled. The pro-inflammatory cytokine IL-6, IL-2, IFN-γ, TNF-α, anti-inflammatory cytokines IL-4 and IL-10 in serum were analyzed by flow cytometry microsphere array (CBA). Results: We found that the levels of TNF-α and IL-10 in patients with lung cancer, COPD and pneumonia were significantly higher than control group. The IL-6 in the lung cancer group were significantly increased compared with the controls and COPD group, pneumonia group. IFN-γ and IL-2 levels were lower in lung cancer compared with controls and COPD group, pneumonia group. TNF-α, IL-4 and IL-10 levels were increased in patients with COPD and pneumonia compared with controls. In addition, the concentrations of IFN-γ and IL-6 were increased in acute exacerbation COPD (AECOPD) group compared with stable COPD group. Conclusion: In conclusion, elevated TNF-α and IL-10 levels in serum may be related with lung diseases including lung cancer, COPD and pneumonia. Additionally, IFN-γ and IL-6 might be potential biomarkers for the further deterioration of lung disease patients. The increased concentrations of IFN-γ and IL-6 might be used to predict the exacerbation of COPD.


Foods ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 58
Author(s):  
Jeong-Ho Kim ◽  
Yeong-Seon Won ◽  
Hyun-Dong Cho ◽  
Seong-Min Hong ◽  
Kwang-Deog Moon ◽  
...  

The fruit of Prunus mume (PM) is widely cultivated in East Asia, and it has been used as a folk medication for gastrointestinal disorders, e.g., diarrhea, stomach ache and ulceration. In this study, the pectinase-treated PM juice (PJ) was fermented with Lactobacillus strains containing fundamental organic acids and free amino acids. The PJ fermented with Lactobacillus plantarum and L. casei (FP) was investigated for its protective effect in dextran sodium sulfate (DSS)-induced colitis mice model. The administration of FP reduced lipid peroxidation and histopathological colitis symptoms, e.g., shortening of the colon length, depletion of mucin, epithelial injury and ulceration, in colonic tissues. The FP-supplemented group showed the alleviation of pro-inflammatory cytokines. Compared with the DSS control group, the supplementation of FP significantly reduced the levels of serum interferon-γ (IFN-γ), interleukin (IL)-1β, IL-6, IL-12 and IL-17 as well as colonic tumor necrosis factor-α, IFN-γ, IL-12 and IL-17. Furthermore, the DSS-induced TUNEL-positive area was significantly reduced by the FP supplementation. These results show that the supplementation of FP fermented with mixed lactic acid bacteria, L. plantarum and L. casei, elucidated the protective effect in DSS-induced colitis mice. Hence, this study suggests that FP can be utilized as a natural therapeutic agent for colitis and intestinal inflammation.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Kyoungwon Cho ◽  
Sung Sun Park ◽  
Hakjoo Choi

Chrysanthemum morifolium Ramatuelle and Scutellaria baicalensis Georgi (skullcap) have been used as safe raw materials for drinking or as traditional medicines in Korea. In this study, we investigated the potential therapeutic effects of ovalbumin-induced asthma in a mouse model. After establishing the model, mice were treated with a mixture of chrysanthemum and skullcap extracts at different mixing ratios (6 : 4, 7 : 3, and 8 : 2). Immune cell counts and the production of various inflammatory cytokines were measured using biochemical tests. Among the mixtures tested, the 7 : 3 ratio (CS73) showed the most pronounced effects. CS73 significantly reduced the levels of the inflammatory cytokines interleukin- (IL-) 1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, and IL-17E in the serum and bronchoalveolar lavage fluid of asthmatic mice. In addition, CS73 treatment significantly increased the production of IL-2 and interferon-γ and decreased the production of immunoglobulin E, histamine, and thymic stromal lymphopoietin in asthmatic mice compared to the control group. Our results suggest that the combination of chrysanthemum and skullcap extracts, especially at a 7 : 3 ratio, can be used to improve bronchial health and contribute to improved public health.


2021 ◽  
Author(s):  
De-Huan Xie ◽  
Yi-Chuan Li ◽  
Sai Ma ◽  
Xin Yang ◽  
Ruo-Ming Lan ◽  
...  

Abstract Purpose: Ultra-high dose rate FLASH irradiation has been shown to cause less normal tissue damage compared with conventional irradiation, also termed “FLASH effect”. However, the underlying mechanism was scarcely known. The purpose of the present study was to determine whether FLASH and conventional irradiation would induce differential inflammatory cytokines expression. Materials and methods: Female FvB mice were randomly assigned to three different groups: non-irradiated control, conventional (CONV) and FLASH groups. Mice were irradiated at 6 to 19 Gy of CONV (0.1 Gy/s) or FLASH (38.5-600 Gy/s) irradiation using an Elekta Synergy linac (6 MeV). Mice were immobilized in prone position in a custom-designed applicator with dosimetry films positioned under the body. Dose were verified by Gafchromic films. Enzyme linked immunosorbent assay (ELISA) were performed in serum samples of the mice at 6, 18 and 31 days after irradiation for four inflammatory cytokines: tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6) and IL-10. Flow cytometry using antibodies for CD3, CD8, CD4 and CD45 in blood were performed pre- and 1-week post irradiation. Results: At D6 (18-19 Gy), both IL-6 and TNF-α were elevated, and IL-10 was reduced in FLASH and CONV group, while IFN-γ was only significantly increased in conventional group, compared with control group. At D18 (10 Gy) and D31 (13-19 Gy), conventional RT significantly elevated levels of IL-6, IFN-γ and TNF-α and reduced IL-10 level compared with FLASH group and control group. Additionally, even low dose conventional irradiation (13 Gy) could induce higher level of pro-inflammatory cytokines and lower level of anti-inflammatory cytokine than high dose (17-19 Gy) FLASH irradiation at D31. Flow cytometry showed that the CD8+/CD45+ ratio in the blood were higher in the conventional than in FLASH. These data indicate that minor inflammatory cytokine levels of serum in FLASH could be result of the absent of immune overactivation induced by conventional irradiation. Conclusions: Ultra-high dose rate electron FLASH caused less inflammatory cytokine levels of serum which might be a result from less CD8+/CD45+ ratio in the blood. Thus, differential cytokines and CD8+ T cell expression between FLASH and conventional irradiation would be a potential mechanism for “FLASH effect”.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5527-5527
Author(s):  
Manuel Schmidt ◽  
Javier de Cristobal ◽  
Astrid Sander ◽  
Bernadette Brzezicha ◽  
Sven A. Koenig-Merediz ◽  
...  

Abstract Cytosine-guanine (CpG) motifs containing oligonucleotides (ODN) are commonly used for immunomodulatory purpose in cancer therapy and for the treatment of allergic diseases since they resemble bacterial DNA and serve as “danger signals”. These CpG-ODNs promote predominately a TH1-response with secretion of IL-12 and IFN-γ, In addition their broad potential includes activation of B-cell proliferation, monocyte stimulation and secretion of IgM and IL-6, and stimulation of plasmacytoid DC to produce IFN-α/-β and thus γδT-cells and NK-cells to express CD69 and secrete IFN-γ. Usually phosphorothioate (PS) modifications are to enhance the stability, but these are leading to several side-effects, like severe organ enlargements, morphological changes and immunosuppression in mice. We designed immunomodulatory molecules based on short covalently-closed dumbbell-like structures (dSLIM) to stabilize the DNA without the otherwise necessary PS-modification. To evaluate the anti-tumor effect of the dSLIM molecules we developed an in vitro anti-tumor assay. This assay uses supernatant from dSLIM-activated human PBMCs for incubation with tumor cells in vitro. We observed increased apoptosis and necrosis by the HT-29 tumor cell line after incubation with supernatant from dSLIM-treated PBMC which was significantly higher than the effect of supernatant from non-treated PBMC. In addition, supernatant from dSLIM-treated PBMC increased the expression of HLA-ABC on the tumor cells, a pre-requisite for tumor cell recognition by the immune system. These effects were confirmed with human HEK293 and murine Renca cell lines. Analyzing the effect with neutralizing antibodies to various apoptosis-related cytokines, we observed a crucial role of IFN-γ but not IFN-α or TNFα. To investigate the anti-tumor effects of dSLIM in vivo, we employed a SKH1 murine model which is prone to spontaneous development of papillomas. Using chemicals for initiation and weekly promotion of de novo papilloma development we compared groups of weekly s.c. or i.p. dSLIM injections, respectively, with the PBS control group. The number of papilloma developing mice was significantly lower in the dSLIM groups and the total number of papillomas on all mice was reduced by approximately 50%. In conclusion, we showed that dSLIM immunomodulators exhibit potent anti-tumor effects in vitro and in vivo.


2019 ◽  
Vol 18 ◽  
pp. 153473541984079 ◽  
Author(s):  
Peiying Yang ◽  
Yan Jiang ◽  
Patrea R. Rhea ◽  
Tara L. Conway ◽  
Dongmei Chen ◽  
...  

Biofield therapies have gained popularity and are being explored as possible treatments for cancer. In some cases, devices have been developed that mimic the electromagnetic fields that are emitted from people delivering biofield therapies. However, there is limited research examining if humans could potentially inhibit the proliferation of cancer cells and suppress tumor growth through modification of inflammation and the immune system. We found that human NSCLC A549 lung cancer cells exposed to Sean L. Harribance, a purported healer, showed reduced viability and downregulation of pAkt. We further observed that the experimental exposure slowed growth of mouse Lewis lung carcinoma evidenced by significantly smaller tumor volume in the experimental mice (274.3 ± 188.9 mm3) than that of control mice (740.5 ± 460.2 mm3; P < .05). Exposure to the experimental condition markedly reduced tumoral expression of pS6, a cytosolic marker of cell proliferation, by 45% compared with that of the control group. Results of reversed phase proteomic array suggested that the experimental exposure downregulated the PD-L1 expression in the tumor tissues. Similarly, the serum levels of cytokines, especially MCP-1, were significantly reduced in the experimental group ( P < .05). Furthermore, TILs profiling showed that CD8+/CD4− immune cell population was increased by almost 2-fold in the experimental condition whereas the number of intratumoral CD25+/CD4+ (T-reg cells) and CD68+ macrophages were 84% and 33%, respectively, lower than that of the control group. Together, these findings suggest that exposure to purported biofields from a human is capable of suppressing tumor growth, which might be in part mediated through modification of the tumor microenvironment, immune function, and anti-inflammatory activity in our mouse lung tumor model.


2020 ◽  
Vol 8 (3) ◽  
pp. 103-112
Author(s):  
Atefeh SADEGHI SHERMEH ◽  
Majid KHOSHMIRSAFA ◽  
Ali-Akbar DELBANDI ◽  
Payam TABARSI ◽  
Esmaeil MORTAZ ◽  
...  

Introduction: Tuberculosis (TB) and especially resistant forms of it have a substantial economic burden on the community health system for diagnosis and treatment each year. Thus, investigation of this field is a priority for the world health organization (WHO). Cytokines play important roles in the relationship between the immune system and tuberculosis. Genetic variations especially single nucleotide polymorphisms (SNPs) impact cytokine levels and function against TB. Material and Methods: In this research SNPs in IFN-γ (+874 T/A) and IL-10 (-592 A/C) genes, and the effects of these SNPs on cytokine levels in a total of 87 tuberculosis patients and 100 healthy controls (HCs) were studied. TB patients divided into two groups: 1) 67 drug-sensitive (DS-TB) and 2) 20 drug-resistant (DR-TB) according to drug sensitivity test using polymerase chain reaction (PCR). For the genotyping of two SNPs, the PCR-based method was used and IFN-γ and IL-10 levels were measured by ELISA in pulmonary tuberculosis (PTB) and control group. Results: In -592A/C SNP, only two genotypes (AA, AC) were observed and both genotypes showed statistically significant differences between DR-TB and HCs (p=0.011). IL-10 serum levels in PTB patients were higher than HCs (p=0.02). The serum levels of IFN-γ were significantly higher in DS-TB patients than that of the other two groups (p<0.001); however, no significant differences were observed for allele and genotype frequencies in IFN-γ +874. Conclusions: Our results suggest that the SNP at -592 position of IL-10 gene may be associated with the susceptibility to DR-TB. However, further investigation is necessary. Keywords: Polymorphism, IFN-γ, IL-10, tuberculosis, drug-resistant tuberculosis


Sign in / Sign up

Export Citation Format

Share Document