Glucocorticoid sensitivity of interleukin-1 agonist and antagonist secretion: the effects of age and gender

2000 ◽  
Vol 278 (4) ◽  
pp. R855-R862 ◽  
Author(s):  
Jane M. Daun ◽  
Richard W. Ball ◽  
Joseph G. Cannon
Keyword(s):  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Dependent Manner ◽  
Basal Secretion ◽  
Peripheral Blood Mononuclear ◽  
Age Related ◽  
Agonist And Antagonist ◽  
And Gender ◽  
Dose Dependent ◽  
Pituitary Adrenal Axis

Interleukin-1 (IL-1) is a primary mediator of inflammation that is regulated, in part, by the hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine if gender- or age-related differences exist in the sensitivity of IL-1-producing cells to hydrocortisone. Peripheral blood mononuclear cells (PBMC) isolated from men and women (21–77 yr old) were incubated with hydrocortisone (0, 50, 100, 500, or 1,000 ng/ml) with or without lipopolysaccharide (LPS). Secretion of IL-1β and IL-1 receptor antagonist was inhibited in a dose-dependent manner ( P = 0.001) without age- or gender-related differences. Hydrocortisone decreased soluble IL-1 receptor type II (sIL-1RII) secretion by unstimulated cells ( P = 0.0001), but it increased secretion by LPS-stimulated cells ( P = 0.0001) in all groups. Unstimulated cell supernatants from men contained greater concentrations of sIL-1RII than the supernatants from women ( P= 0.011). Compared with men, PBMCs from women were less responsive to hydrocortisone inhibition of sIL-1RII secretion, regardless of age ( P = 0.001), and compared with the follicular phase, sIL-1RII secretion was lower in the luteal phase of the menstrual cycle ( P < 0.05). These data indicate that basal secretion and glucocorticoid modulation of sIL-1RII secretion by cultured PBMCs are gender dependent. Moreover, glucocorticoid influences on sIL-1RII secretion depend on the presence or absence of gram-negative bacterial toxins.

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.

A Fully Human Antagonist Anti-CD40 Antibody Triggers Significant Antitumor Activity Against Human Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2414-2414
Author(s):  
Yu-Tzu Tai ◽  
Xian-Feng Li ◽  
Xia Tong2 ◽  
Laurence Catley ◽  
Daniel Santos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Lines ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Specific Lysis ◽  
Growth And Survival ◽  
Human Multiple Myeloma ◽  
Dose Dependent

Abstract We previously demonstrated that CHIR-12.12, a fully human anti-CD40 mAb (IgG1) generated in XenoMouseÒ mice (Abgenix, Inc), blocks CD40/CD40 ligand (CD40L) interactions and has more potent anti-lymphoma activity than Rituximab both in vivo and in vitro (abstract #2386, ASH, San Diego, Dec. 2003). In this study, we assess the efficacy of CHIR-12.12 against human multiple myeloma (MM) using CD40-expressing MM cell lines and purified CD138+ patient cells. CHIR-12.12 binds to purified CD138+ MM cells in &gt;80% (10/12) of patient samples, as measured by flow cytometry: the mean fluorescence intensity (MFI) range was 1 to 20 for CHIR-12.12 vs 0.2–0.9 for control human IgG1. We next examined the antagonist activity of CHIR-12.12 in MM cells. CHIR-12.12 blocked CD40L-mediated proliferation of CD40-expressing MM lines and purified CD138+ patient cells from 2 MM patients in a dose-response manner. In contrast, CHIR-12.12 alone did not alter constitutive MM cell proliferation. Immunoblotting analysis demonstrated that PI3-K/AKT, NF-kB, and ERK activation induced by hCD40L in the 12BM MM cell line was significantly inhibited by CHIR-12.12 (5 μg/ml). Adhesion of MM cells to bone marrow stromal cells (BMSCs) confers growth and survival benefit for tumor cells. Since CD40 activation, either by stimulatory mouse anti-CD40 mAb G28.5 or formaldehyde-fixed CHO cells expressing hCD40L, induces MM cell adhesion to fibronectin (FN) or BMSCs, we next asked whether antagonist CHI12.12 abrogates this process. CHIR-12.12 inhibited CD40L-induced adhesion of MM cell lines to FN in a dose dependent manner (0.001-10 μg/ml), whereas control human IgG did not. Moreover, CHIR-12.12 (1 μg/ml) blocked hCD40L-induced adhesion of freshly isolated patient MM cells to BMSCs. Adhesion of MM cells to BMSCs induces IL-6 secretion, an important growth and survival cytokine for MM cells, and treatment of MM cells with hCD40L further augmented adhesion-induced IL-6 secretion. Conversely, pretreatment of CD40-expressing MM cell lines with CHIR-12.12 significantly decreased IL-6 secretion triggered by coculture of MM cells with BMSCs. We next examined whether CHIR-12.12 stimulates antibody-dependent cellular cytotoxicity (ADCC) against CD40-expressing MM cells. Human peripheral blood mononuclear cells and purified NK cells (CD56+CD3−) were used as effector cells. CHIR-12.12 triggered MM cell lysis in a dose dependent manner, as measured in CD40-expressing MM cell lines. The maximum specific lysis of 20–70 % was achieved at 10 μg/ml concentration of CHIR-12.12. CHIR-12.12 mediated lysis was specific to CD40-expressing MM cells, as CHIR-12.12 did not induce ADCC against CD40-negative MM cells. Importantly, CHIR-12.12 induced ADCC against CD138+ cells isolated from 2 MM patients. These results provide preclinical rationale for clinical evaluation of CHIR-12.12 with the goal of improving patient outcome in MM.

scholarly journals Metformin improves cognition of aged mice by promoting cerebral angiogenesis and neurogenesis

2020 ◽  
Author(s):  
Xiaoqi Zhu ◽  
Junyan Shen ◽  
Shengyu Feng ◽  
Ce Huang ◽  
Zhongmin Liu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Vascular Density ◽  
Aged Mouse ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Age Related ◽  
Glycolysis Pathway

AbstractThe cerebral microvasculature is essential for preservation of normal cerebral function. Age-related decreases of neurogenesis and cognitive function are accompanied by reduced blood flow and a decline in neural stem cell (NSC) number. Here, we report that metformin administered by tail vein injection enhanced cognition in aged but not young mice in a dose-dependent manner. Further, metformin restored cerebral blood flow and brain vascular density and promoted neurogenic potential of the subependymal zone/subventricular zone both in vivo and in vitro. RNA-Seq result indicated that metformin could enhance glycolysis in blood, with an increase in relative mRNA expression of the enzyme in the glycolysis pathway from hippocampal tissue of metformin-treated mice. Mechanistically, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme in the glycolysis pathway, may contribute to angiogenic and neurogenic potentials of NSCs. Interestingly, examination of peripheral blood mononuclear cells from people of various ages showed that mRNA expression of GAPDH gradually decreased with age, while its expression level positively correlated with cognitive levels. Our results indicate that metformin represents a candidate pharmacological approach for recruitment of NSCs in aged mouse brain by enhancing glycolysis and promoting neurovascular generation, a strategy that might be of therapeutic value for anti-aging in humans.Graphical Abstract

Fibronectin modulates expression of interleukin-1 beta and its receptor antagonist in human mononuclear cells

1996 ◽  
Vol 271 (1) ◽  
pp. L61-L69 ◽  
Author(s):  
K. L. Graves ◽  
J. Roman
Keyword(s):  
Receptor Antagonist ◽  
Type I Collagen ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 1 ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Human Mononuclear Cells ◽  
Naturally Occurring ◽  
Dose Dependent

Identification of factors that regulate production of proinflammatory cytokines may provide insight into mechanisms governing lung inflammation. One potential regulatory factor highly expressed in inflamed tissues is fibronectin (FN). To determine the potential effects of FN on interleukin (IL)-1 beta production, we exposed human peripheral blood mononuclear cells to soluble FN. This treatment resulted in the accumulation of IL-1 beta mRNA and enhancement of IL-1 beta protein synthesis and secretion. This effect was dose dependent and appeared to be mediated by the integrin alpha 5 beta 1. Treatment with FN also increased production of IL-1 receptor antagonist (IL-1ra), a naturally occurring inhibitor of IL-1 function. However, the stimulatory effect of FN on IL-1ra production was abolished by costimulation with type I collagen. We conclude that the increased deposition of FN in injured tissues may enhance the expression of IL-1 beta mRNA and augment the production and release of IL-1 beta protein by mononuclear cells. Differential expression of IL-1 beta and IL-1ra resulting in a high IL-1 beta-to-IL-1ra ratio in response to mixed matrices containing FN and type I collagen may be an important regulatory point in inflammation.

Effects of the Neuropeptide, Substance P, on Lymphocyte Proliferation in Rheumatoid Arthritis

1995 ◽  
Vol 23 (6) ◽  
pp. 431-438 ◽  
Author(s):  
M Jovas ◽  
L A Pinto ◽  
J A Pereira da Silva ◽  
R M M Victorino
Keyword(s):  
Rheumatoid Arthritis ◽  
Substance P ◽  
Lymphocyte Proliferation ◽  
Mononuclear Cells ◽  
Thymidine Incorporation ◽  
Lymphocyte Activation ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Dose Dependent

There is evidence supporting the involvement of the neuropeptide, substance P, in the pathogenesis of rheumatoid arthritis. In view of the suggested role of T-cells in this disease, we have investigated the effects of substance P on mitogen-induced lymphocyte proliferation in rheumatoid arthritis patients. The peripheral blood mononuclear cells from 20 patients with rheumatoid arthritis and 25 controls were cultured in the presence or absence of substance P (10−-10 M to 10−-6 M) and stimulated with phytohaemagglutinin or concanavalin A. After 3 days of culture the proliferative responses were determined by measuring [3H]thymidine incorporation into the cells. Substance P enhanced, in a dose-dependent manner, the lymphocyte proliferative responses both in rheumatoid arthritis patients and in controls. Although there was a trend towards a greater enhancing effect in the rheumatoid arthritis patients, this was not statistically significant. Some individual patients with rheumatoid arthritis showed enhancements of lymphocyte proliferation with substance P that were clearly outside the range seen in healthy controls. The possibility that substance P has a role in the pathogenesis of rheumatoid arthritis through the up-regulation of lymphocyte activation should be considered in further studies of the immunomodulatory properties of substance P in arthritis.

scholarly journals Activation of IL-10+ B cells: A novel immunomodulatory mechanism for therapeutic bacterial suspensions

2020 ◽  
Vol 8 ◽  
pp. 205031212090154 ◽  
Author(s):  
Alberto Salazar ◽  
Jane E Nieto ◽  
Henry Velazquez-Soto ◽  
Maria C Jiménez-Martínez
Keyword(s):  
B Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Bacterial Suspension ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Bacterial Lysates ◽  
Dose Dependent

Objectives: Bacterial components are used to improve immune responses in patients with respiratory infections. Pharmacological formulations of bacterial components include a mixture of bacterial antigens, some of which are complete inactivated bacteria, that is, named bacterial suspensions; while others are fragments of bacteria, which are presented as bacterial lysates. Although bacterial lysates have been broadly used as immune-stimulators, the biological support for the therapeutic effectiveness of bacterial suspension has not yet been studied. Thus, the aim of our study was to investigate the immunological activity induced by bacterial suspension. Methods: This work was an exploratory translational study. Peripheral blood mononuclear cells were obtained from healthy donors and cultured in time–dose dependent assays with a commercial bacterial suspension. Flow cytometry was used for phenotypic analysis and for determining soluble cytokines in culture supernatants. Results: We observed that bacterial suspension activates B cells in a dose-dependent manner. Peripheral blood mononuclear cells were able to secrete IL-6 and IL-10 after 24 h of bacterial suspension stimulation. TLR2 expression was observed mainly on CD19+ CD38Lo B cells after 72 h of culture; remarkably, most of the TLR2+ CD19+ cells were also IL-10+. Conclusion: Our findings suggest that bacterial suspension induces the activation of B cell subsets as well as the secretion of IL-6 and IL-10. Expression of TLR2 on CD19+ cells could act as an activation loop of IL-10+ B regulatory cells. The clinical implications of these findings are discussed at the end of this article.

Halofuginone, an Old Anticoccidosis Drug, Induces Apoptosisin Multiple Myeloma Cells, Associated with Down Regulation of MCL1.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4786-4786
Author(s):  
Merav Leiba ◽  
Yu-Tzu Tai ◽  
Teru Hideshima ◽  
Jana Jakubikova ◽  
Ikeda Hiroshi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Mononuclear Cells ◽  
Matrix Metalloproteinase 2 ◽  
Type I ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Dose Dependent

Abstract Halofuginone, a synthetic derivative of quinazolinone alkaloid, has recently been shown to have an anti-cancer effect in various solid and hematological malignancies. It is an orally available drug with a safe toxicity profile in clinical trials of inflammatory disease and has anti-angiogenic, anti-metastatic and anti-proliferative effects in preclinical studies. It blocks TGFb signaling by targeting Smad 2/3, inhibits NFkB activity, as well as downregulates extra cellular matrix (ECM) formation via the inhibition of collagen type I formation and matrix metalloproteinase 2(MMP2). Since ECM has an important role in the bone marrow microenvironment in multiple myeloma (MM) pathogenesis, we here examined whether halofuginone induces cytotoxicity against various MM cell lines, including those sensitive and resistant to conventional and novel chemotherapies. Halofuginone (12.5–400 nM) induced cytotoxicity in a dose-dependent fashion in a variety of MM cell lines (n=20), regardless of the sensitivity to conventional chemotherapy (i.e., dexamethasone, melphalan, doxorubicin) and novel therapies (i.e., lenalidomide, bortezomib) with IC50 of 50–200 nM. In contrast, halofuginone did not induce cytotoxicity against CD40-activated peripheral blood mononuclear cells from normal donors, even at high doses (500–1000nM). Importantly, neither IL6 nor IGF1, two key growth and survival factors in MM, overcame the growth inhibitory effect of halofuginone. We further examined molecular mechanisms whereby halofuginone triggers growth inhibition in MM cells. It induced both apoptosis and necrosis in a time- (2–48h) and dose (50–200 nM) dependent manner in MM1R and OPM1 MM cells, assessed by annexin V/ PI staining. Significant dose- dependent activation of caspase 3 and 8 was demonstrated after 25–200 nM of halofuginone treatment of MM1R, MM1S, and OPM1 cells. Mitochondrial membrane potential was also reduced after 24 hours of halofuginone treatment (50, 200 nM) of MM1R and OPMI cells, as evident by the accumulation of JC1 monomers. In addition, western blot analysis showed that halofuginone induces cleavage of apoptotic proteins caspase 3/8 and PARP, and downregulates anti-apoptotic protein MCL1. Taken together, these data suggest that halofuginone has significant anti-MM activities and is a potential novel therapy in MM.

scholarly journals Effect of interleukin-1 (IL-1) blockade on cytokine synthesis: II. IL-1 receptor antagonist inhibits lipopolysaccharide-induced cytokine synthesis by human monocytes

Blood ◽  
1992 ◽  
Vol 79 (9) ◽  
pp. 2364-2369 ◽  
Author(s):  
EV Granowitz ◽  
E Vannier ◽  
DD Poutsiaka ◽  
CA Dinarello
Keyword(s):  
Receptor Antagonist ◽  
Messenger Rna ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Cytokine Synthesis

Abstract Lipopolysaccharide (LPS) stimulates interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) gene expression and synthesis in human peripheral blood mononuclear cells (PBMC). IL-1 can also induce PBMC to synthesize IL-1 and TNF alpha. In the present study, we used IL- 1 receptor antagonist (IL-1ra) to determine the relative contribution of an IL-1-positive feedback loop to the total amount of LPS-induced cytokine synthesis. Pretreatment of PBMC with human recombinant IL-1ra reduced LPS-induced cytokine synthesis in a dose-dependent manner (P less than .001). Maximal inhibition was 33% for IL-1 alpha (P less than .01), 43% for IL-1 beta (P = .001), and 20% for TNF alpha (P less than .05). We consistently observed IL-1ra suppression of LPS-induced cytokines in PBMC of 38 volunteers. However, this phenomenon was not specific for LPS; 1 microgram/mL IL-1ra inhibited IL-1 beta synthesized in response to human recombinant IL-2 by 44% (P less than .001), toxic shock syndrome toxin-1 by 26% (P less than .05), and phorbol 12- myristate 13-acetate by 76% (P less than .001). IL-1ra added to PBMC 4 or 8 hours after stimulation with LPS still inhibited IL-1 beta synthesis by 44% (P less than .001) or 25% (P = .01), respectively. The steady state messenger RNA levels of IL-1 beta were reduced in PBMC stimulated by LPS in the presence of IL-1ra. In monocytes isolated by elutriation, IL-1ra reduced LPS-induced IL-1 alpha by 16% (P less than .001), IL-1 beta by 14% (P less than .05), and TNF alpha by 24% (P = .01). We conclude that IL-1-induced IL-1 significantly contributes to LPS-induced cytokine synthesis.

Inhalation Anesthetics Induce Apoptosis in Normal Peripheral Lymphocytes In Vitro 

2001 ◽  
Vol 95 (6) ◽  
pp. 1467-1472 ◽  
Author(s):  
Hiroshi Matsuoka ◽  
Shin Kurosawa ◽  
Takashi Horinouchi ◽  
Masato Kato ◽  
Yasuhiko Hashimoto
Keyword(s):  
Caspase 3 ◽  
Mononuclear Cells ◽  
Time Dependent ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Normal Peripheral Blood ◽  
Inhalation Anesthetics ◽  
Peripheral Lymphocytes ◽  
Dose Dependent

Background The authors hypothesized that perioperative lymphocytopenia is partially caused by apoptosis of lymphocytes induced by inhalation anesthetics. Therefore, they evaluated whether sevoflurane and isoflurane induce apoptosis of normal peripheral lymphocytes. Methods Normal peripheral blood mononuclear cells were exposed to sevoflurane and isoflurane, and the percentages of apoptotic lymphocytes was measured by Annexin V-fluorescein isothiocyanate-7-amino actinomycin D flow cytometry after 24 h of exposure (0.5, 1.0, and 1.5 mm) and after 6, 12, and 24 h of exposure (1.5 mm). The percentages of lymphocytes with caspase 3-like activity were also measured after 24 h of exposure (1.5 mm). Results The percentages of apoptotic lymhocytes were increased in a dose-dependent manner (controls: 5.1 +/- 1.4%; sevoflurane: 7.3 +/- 1.3% [0.5 mm], 9.1 +/- 1.5% [1.0 mm], 12.6 +/- 2.1% [1.5 mm]; isoflurane: 7.5 +/- 1.6% [0.5 mm], 10.5 +/- 1.5% [1.0 mm], 16.3 +/- 2.7% [1.5 mm]) after 24 h of exposure and in a time-dependent manner (controls: 1.2 +/- 0.4% [6 h], 3.4 +/- 0.7% [12 h], 5.6 +/- 1.2% [24 h]; sevoflurane: 1.8 +/- 0.4% [6 h], 6.4 +/- 1.2% [12 h], 11.3 +/- 2.2% [24 h]; isoflurane: 2.6 +/- 0.5% [6 h], 8.8 +/- 1.5% [12 h],16.0 +/- 1.9% [24 h]) at the concentration of 1.5 mm. The percentages of lymphocytes with caspase 3-like activity were increased (controls: 10.0 +/- 1.1%; sevoflurane: 13.8 +/- 1.2%; isoflurane: 17.0 +/- 1.3%). Conclusions Both sevoflurane and isoflurane induced apoptosis in peripheral lymphocytes in dose-dependent and time-dependent manners in vitro.

Anti-Inflammatory Effect of Dohongsamultang through Inhibition of Nuclear Factor-κB Activation in Peripheral Blood Mononuclear Cells of Patients with Cerebral Infarction

2007 ◽  
Vol 35 (03) ◽  
pp. 415-426 ◽  
Author(s):  
Su-Jin Kim ◽  
Hyun-Ja Jeong ◽  
Sei-Uk Park ◽  
Byung-Soon Moon ◽  
Phil-Dong Moon ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Mononuclear Cells ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory Reactions ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Inflammatory Effect

The Korean indigenous medicine "Dohongsamultang (DHSMT)" has long been used for various cerebrovascular diseases. However, the exact mechanism for the anti-inflammatory effect of DHSMT is not completely understood. The aim of the present study is to elucidate how DHSMT modulates the inflammatory reaction in lipopolysaccaride (LPS)-stimulated peripheral mononuclear cells from cerebral infarction (CI) patients. Production and expression of cytokine was measured via the ELISA and RT-PCR methods. The level of nuclear factor-kappa B (NF-κB)/Rel A protein and NF-κB DNA binding activity were determined via the Western blot analysis and transcription factor enzyme-linked immunoassay. It showed that DHSMT inhibited the production of TNF-α, IL-1β, and IL-6 induced by LPS in a dose-dependent manner ( p < 0.05). The maximal inhibition rates for TNF-α, IL-1β, and IL-6 production by DHSMT were about 50.18%, 32.13%, and 38.03%, respectively. DHSMT inhibited the TNF-α mRNA expression in a dose-dependent manner. We also showed that the inhibitory effect of DHSMT is through the suppression of the NF-κB pathway. The study suggests an important molecular mechanism by GMGHT to reduce inflammation, which might explain its beneficial effect in the regulation of inflammatory reactions.

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