scholarly journals Effect of Orally AdministeredAtractylodes macrocephalaKoidz Water Extract on Macrophage and T Cell Inflammatory Response in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Tae-Kyung Kwak ◽  
Hyung-Seok Jang ◽  
Mi-Gi Lee ◽  
Young-Sung Jung ◽  
Dae-Ok Kim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inflammatory Response ◽  
T Cell Activation ◽  
Inflammatory Responses ◽  
Water Extract ◽  
Peritoneal Macrophages ◽  
Functional Responses ◽  
Th2 Response ◽  
Anti Inflammatory

The rhizome ofAtractylodes macrocephalaKoidz (AM) is a constituent of various Qi booster compound prescriptions. We evaluated inflammatory responses in macrophages and T cells isolated from mice following oral administration of AM water extract (AME). Peritoneal exudate cells were isolated from thioglycollate-injected mice and alterations in scavenger receptors were examined. Peritoneal macrophages were stimulated with lipopolysaccharide (LPS). Serum cytokine responses to intraperitoneal LPS injection were also evaluated. Splenocytes were isolated and their composition and functional responses were measured. The content of atractylenolide I and atractylenolide III, known anti-inflammatory ingredients, in AME was 0.0338 mg/g extract and 0.565 mg/g extract, respectively. AME increased the number of SRA(+)CD11b(+) cells in response to thioglycollate. Peritoneal macrophages isolated from the AME group showed no changes in inflammatory markers such as tumor necrosis factor- (TNF-)α, interleukin- (IL-) 6, inducible nitric oxide synthase, and cyclooxygenase-2 but exhibited a decrease in CD86 expression. Interestingly, AME decreased the serum levels of TNF-αand IL-6 upon intraperitoneal injection of LPS. Regarding the adaptive immune system, AME increased the CD4(+) T cell population and major histocompatibility complex class II molecule expression in the spleen, and cultured splenocytes from the AME group showed increased production of IL-4 concurrent with decreased interferon-γproduction during T cell activation. AME promoted the replenishment of peritoneal macrophages during the inflammatory response but its anti-inflammatory activity did not appear to be mediated by the modulation of macrophage activity. AME also altered the immune status of CD4 T cells, promoting the Th2 response.

scholarly journals Probiotic supplementation reduces inflammatory profiles but does not prevent oral immune perturbations during SIV infection

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rhianna Jones ◽  
Kyle Kroll ◽  
Courtney Broedlow ◽  
Luca Schifanella ◽  
Scott Smith ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Rhesus Macaques ◽  
Oral Microbiome ◽  
Probiotic Supplementation ◽  
Siv Infection ◽  
Anti Inflammatory

AbstractHIV/SIV infections lead to massive loss of mucosal CD4 + T cells and breakdown of the epithelial mucosa resulting in severe microbial dysbiosis and chronic immune activation that ultimately drive disease progression. Moreover, disruption of one of the most understudied mucosal environments, the oral cavity, during HIV-induced immunosuppression results in significant microbial and neoplastic co-morbidities and contributes to and predicts distal disease complications. In this study we evaluated the effects of oral probiotic supplementation (PBX), which can stimulate and augment inflammatory or anti-inflammatory pathways, on early SIV infection of rhesus macaques. Our study revealed that similar to the GI mucosae, oral CD4 + T cells were rapidly depleted, and as one of the first comprehensive analyses of the oral microflora in SIV infection, we also observed significant modulation among two genera, Porphyromonas and Actinobacillus, early after infection. Interestingly, although PBX therapy did not substantially protect against oral dysbiosis or ameliorate cell loss, it did somewhat dampen inflammation and T cell activation. Collectively, these data provide one of the most comprehensive evaluations of SIV-induced changes in oral microbiome and CD4 + T cell populations, and also suggest that oral PBX may have some anti-inflammatory properties in lentivirus infections.

scholarly journals p38/AP-1 Pathway in Lipopolysaccharide-Induced Inflammatory Responses Is Negatively Modulated by Electrical Stimulation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Deok Jeong ◽  
Jaehwi Lee ◽  
Young-Su Yi ◽  
Yanyan Yang ◽  
Kyoung Won Kim ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Inflammatory Response ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Physiological Role ◽  
Peritoneal Macrophages ◽  
Cellular Level ◽  
Transcriptional Level ◽  
Weak Current ◽  
Anti Inflammatory

Electrical stimulation with a weak current has been demonstrated to modulate various cellular and physiological responses, including the differentiation of mesenchymal stem cells and acute or chronic physical pain. Thus, a variety of investigations regarding the physiological role of nano- or microlevel currents at the cellular level are actively proceeding in the field of alternative medicine. In this study, we focused on the anti-inflammatory activity of aluminum-copper patches (ACPs) under macrophage-mediated inflammatory conditions. ACPs generated nanolevel currents ranging from 30 to 55 nA in solution conditions. Interestingly, the nanocurrent-generating aluminum-copper patches (NGACPs) were able to suppress both lipopolysaccharide-(LPS-) and pam3CSK-induced inflammatory responses such as NO and PGE2production in both RAW264.7 cells and peritoneal macrophages at the transcriptional level. Through immunoblotting and immunoprecipitation analyses, we found that p38/AP-1 could be the major inhibitory pathway in the NGACP-mediated anti-inflammatory response. Indeed, inhibition of p38 by SB203580 showed similar inhibitory activity of the production of TNF-αand PGE2and the expression of TNF-αand COX-2 mRNA. These results suggest that ACP-induced nanocurrents alter signal transduction pathways that are involved in the inflammatory response and could therefore be utilized in the treatment of various inflammatory diseases such as arthritis and colitis.

scholarly journals Protease-Activated Receptor 2 Has Pivotal Roles in Cellular Mechanisms Involved in Experimental Periodontitis

2009 ◽  
Vol 78 (2) ◽  
pp. 629-638 ◽  
Author(s):  
David M. Wong ◽  
Vivian Tam ◽  
Roselind Lam ◽  
Katrina A. Walsh ◽  
Liliana Tatarczuch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mast Cells ◽  
Bone Resorption ◽  
Inflammatory Response ◽  
T Cell Activation ◽  
Interleukin 2 ◽  
Wild Type ◽  
Periodontal Tissues ◽  
Protease Activated Receptor 2

ABSTRACT The tissue destruction seen in chronic periodontitis is commonly accepted to involve extensive upregulation of the host inflammatory response. Protease-activated receptor 2 (PAR-2)-null mice infected with Porphyromonas gingivalis did not display periodontal bone resorption in contrast to wild-type-infected and PAR-1-null-infected mice. Histological examination of tissues confirmed the lowered bone resorption in PAR-2-null mice and identified a substantial decrease in mast cells infiltrating the periodontal tissues of these mice. T cells from P. gingivalis-infected or immunized PAR-2-null mice proliferated less in response to antigen than those from wild-type animals. CD90 (Thy1.2) expression on CD4+ and CD8+ T-cell-receptor β (TCRβ) T cells was significantly (P < 0.001) decreased in antigen-immunized PAR-2-null mice compared to sham-immunized PAR-2-null mice; this was not observed in wild-type controls. T cells from infected or antigen-immunized PAR-2-null mice had a significantly different Th1/inflammatory cytokine profile from wild-type cells: in particular, gamma interferon, interleukins (interleukin-2, -3, and -17), granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha demonstrated lower expression than wild-type controls. The absence of PAR-2 therefore appears to substantially decrease T-cell activation and the Th1/inflammatory response. Regulation of such proinflammatory mechanisms in T cells and mast cells by PAR-2 suggests a pivotal role in the pathogenesis of the disease.

scholarly journals Preconditioning Enhances the Therapeutic Effects of Mesenchymal Stem Cells on Colitis Through PGE2-Mediated T-Cell Modulation

2018 ◽  
Vol 27 (9) ◽  
pp. 1352-1367 ◽  
Author(s):  
Fu Yuan Yang ◽  
Rui Chen ◽  
Xiaohu Zhang ◽  
Biao Huang ◽  
Lai Ling Tsang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Therapeutic Effect ◽  
T Cell Activation ◽  
Activity Index ◽  
Intraperitoneal Administration ◽  
The Body ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Anti Inflammatory

Mesenchymal stem cell (MSC)-based cell therapy has been demonstrated as a promising strategy in the treatment of inflammatory bowel disease (IBD), which is considered an immune disease. While the exact mechanisms underlying the therapeutic effect of MSCs are still unclear, MSCs display anti-inflammatory and immunomodulatory effects by interacting with various immunoregulatory cells. Our previous studies have shown that MSCs can be preconditioned and deconditioned with enhanced cell survival, differentiation and migration. In this study, we evaluated the effect of preconditioning on the immunoregulatory function of human umbilical cord-derived MSCs (hUCMSCs) and their therapeutic effect on treating IBD. Our results show that intraperitoneal administration of deconditioned hUCMSCs (De-hUCMSCs) reduces the disease activity index (DAI), histological colitis score and destruction of the epithelial barrier, and increases the body weight recovery more intensively than that of un-manipulated hUCMSCs. In addition, De-hUCMSCs but not hUCMSCs elicit anti-apoptotic effects via induction of the ERK pathway during the early stage of IBD development. In vitro co-culture studies indicate that De-hUCMSCs suppress T-cell proliferation and activation more markedly than hUCMSCs. Moreover, De-hUCMSCs block the induction of inflammatory cytokines such as tumor necrosis factor (TNF)α and interleukin (IL)-2, while promoting the secretion of the anti-inflammatory cytokine IL-10 in T-cells. Mechanically, we find that prostaglandin E2 (PGE2) secretion is significantly increased in De-hUCMSCs, the suppression of which dramatically abrogates the inhibitory effect of De-hUCMSCs on T-cell activation, implying that the crosstalk between De-hUCMSCs and T-cells is mediated by PGE2. Together, we have demonstrated that preconditioning enhances the immunosuppressive and therapeutic effects of hUCMSCs on treating IBD via increased secretion of PGE2.

scholarly journals Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Peter A. Szabo ◽  
Hanna Mendes Levitin ◽  
Michelle Miron ◽  
Mark E. Snyder ◽  
Takashi Senda ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interferon Response ◽  
Functional Responses ◽  
Multiple Tumor ◽  
Human T Cell ◽  
Human T Cells

Abstract Human T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences T cell persistence and function. Here, we use single cell RNA-sequencing (scRNA-seq) to define the heterogeneity of human T cells isolated from lungs, lymph nodes, bone marrow and blood, and their functional responses following stimulation. Through analysis of >50,000 resting and activated T cells, we reveal tissue T cell signatures in mucosal and lymphoid sites, and lineage-specific activation states across all sites including distinct effector states for CD8+ T cells and an interferon-response state for CD4+ T cells. Comparing scRNA-seq profiles of tumor-associated T cells to our dataset reveals predominant activated CD8+ compared to CD4+ T cell states within multiple tumor types. Our results therefore establish a high dimensional reference map of human T cell activation in health for analyzing T cells in disease.

scholarly journals Critical role for perforin and Fas-dependent killing of dendritic cells in the control of inflammation

Blood ◽  
2012 ◽  
Vol 119 (1) ◽  
pp. 127-136 ◽  
Author(s):  
Min Chen ◽  
Kumar Felix ◽  
Jin Wang
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Cell Types ◽  
Activated T Cells ◽  
Ifn Γ

AbstractAfter stimulation of antigen-specific T cells, dendritic cell (DCs) are susceptible to killing by these activated T cells that involve perforin and Fas-dependent mechanisms. Fas-dependent DC apoptosis has been shown to limit DC accumulation and prevent the development of autoimmunity. However, a role for perforin in the maintenance of DC homeostasis for immune regulation remains to be determined. Here we show that perforin deficiency in mice, together with the deletion of Fas in DCs (perforin−/−DC-Fas−/−), led to DC accumulation, uncontrolled T-cell activation, and IFN-γ production by CD8+ T cells, resulting in the development of lethal hemophagocytic lymphohistiocytosis. Consistently, adoptive transfer of Fas−/− DCs induced over-activation and IFN-γ production in perforin−/− CD8+ T cells. Neutralization of IFN-γ prevented the spreading of inflammatory responses to different cell types and protected the survival of perforin−/−DC-Fas−/− mice. Our data suggest that perforin and Fas synergize in the maintenance of DC homeostasis to limit T cell activation, and prevent the initiation of an inflammatory cascade.

scholarly journals The Activation Status of Neuroantigen-specific T Cells in the Target Organ Determines the Clinical Outcome of Autoimmune Encephalomyelitis

2004 ◽  
Vol 199 (2) ◽  
pp. 185-197 ◽  
Author(s):  
Naoto Kawakami ◽  
Silke Lassmann ◽  
Zhaoxia Li ◽  
Francesca Odoardi ◽  
Thomas Ritter ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inflammatory Response ◽  
T Cell Activation ◽  
Cell Activation ◽  
Expression Patterns ◽  
Target Tissue ◽  
Autoimmune Encephalomyelitis ◽  
Effector T Cell ◽  
Green Fluorescent

The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)–specific T cells in Lewis rats, whereas transfer of S100β- or myelin oligodendrocyte glycoprotein (MOG)–specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein+ T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo.

scholarly journals Probiotic Supplementation Reduces Inflammatory Profiles But Does Not Prevent Oral Immune Perturbations During SIV Infection

2020 ◽  
Author(s):  
Rhianna Jones ◽  
Kyle Kroll ◽  
Courtney Broedlow ◽  
Luca Schifanella ◽  
Scott Smith ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Rhesus Macaques ◽  
Oral Microbiome ◽  
Probiotic Supplementation ◽  
Siv Infection ◽  
Anti Inflammatory

ABSTRACTHIV/SIV infections lead to massive loss of mucosal CD4+ T cells and breakdown of the epithelial mucosa resulting in severe microbial dysbiosis and chronic immune activation that ultimately drive disease progression. Moreover, disruption of one of the most understudied mucosal environments, the oral cavity, during HIV-induced immunosuppression results in significant microbial and neoplastic co-morbidities and contributes to and predicts distal disease complications. In this study we evaluated the effects of oral probiotic supplementation (Pbx), which can stimulate and augment inflammatory or anti-inflammatory pathways, on early SIV infection of rhesus macaques. Our study revealed that similar to the GI mucosae, oral CD4+ T cells were rapidly depleted, and as one of the first comprehensive analyses of the oral microflora in SIV infection, we also observed significant modulation among two genera, Porphyromonas and Actinobacillus, early after infection. Interestingly, although Pbx therapy did not substantially protect against oral dysbiosis or ameliorate cell loss, it did dampen inflammation and T cell activation. Collectively, these data provide one of the most comprehensive evaluations of SIV-induced changes in oral microbiome and CD4+ T cell populations, and also suggest that oral Pbx could be a simple therapy to improve anti-inflammatory states in addition to more traditional antivirals.

IL-6 Production by B-CLL Cells Plays a Critical Role in the Inhibition of T Cell Activation and Proliferation and Promotes a Th2 Response in Normal T Lymphocytes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2808-2808 ◽  
Author(s):  
Andrea G.S. Buggins ◽  
Piers E.M. Patten ◽  
Julie Richards ◽  
Stephen J. Orr ◽  
Ghulam J. Mufti ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
Critical Role ◽  
Lymphocytic Leukemia ◽  
Th2 Response ◽  
Cytokine Bead Array ◽  
Cd40l Expression

Abstract Immune dysfunction is a hallmark of B-cell chronic lymphocytic leukemia (B-CLL) which occurs through loss of normal cell function as the malignant clone expands, as a result of therapy or because of immunoregulatory properties of the tumor itself. It has previously been shown that B-CLL cells are poor stimulators of the allogeneic mixed lymphocyte reaction (MLR) and we first determined whether this is due to lack of stimulatory activity or active immunosuppression by examining the effect of B-CLL contact and tumor supernatant (TSN) on a 3rd party MLR. Incorporation of B-CLL cells in a 5 day MLR inhibited 3H proliferation by responders in 2/10 cases, whereas TSN inhibited in all 10 cases. Studies in which normal T cells were stimulated by CD3/28 beads for 72 hours in the absence or presence of TSN showed a reduction in cell cycle entry measured by PI and FITC staining with 26+/−4.6% and 13.7+/−4.3% of cells in S +G2M in the absence and presence of TSN respectively (p<0.0001). Studies performed using CFSE labelled normal T cells showed that TSN reduced the number of T cells undergoing one or more cell divisions from a mean of 81.8+/−1.65% to 58.2+/−4.4% (p=0.0072). It is known that T cells in B-CLL have an acquired defect in CD40L expression, which has been ascribed to downregulation by CD40 present on tumor cells. Our experiments confirm that this defect is reversible since purification of B-CLL T cells restores activation induced CD40L upregulation to normal. We further demonstrate that B-CLL TSN from all 17 patients tested inhibits CD40L upregulation by normal T cells in response to PMA and ionomycin or CD3/28 beads (to a mean of 51%+/−5.6%, p<0.0001, of those activated in the absence of TSN) and a parallel inhibition of IL-2 secretion (correlation with CD40L inhibition: p=0.006, r2 = 0.54). In addition to the effects of TSN on T proliferation and activation, B-CLL TSN also induced Th2 polarisation of normal T cells. When activated using CD3/28 beads in control medium, normal T cells show an increase in IL-2, γ-interferon and TNF-α secretion consistent with the expected Th1 response. When incubated in TSN however, 10 and 1000 fold increases in IL-4 and IL6 release were observed respectively consistent with a shift to a Th2 response. B-CLL cells are known to secrete a number of cytokines and in order to determine which might be responsible for the observed effects a number were assayed either by enzyme-linked or cytokine bead array assay. The effects of TSN were not due to TGF-β , IL-10 or soluble CD40 and depletion of soluble CD25 using bead conjugated anti-CD25 had no effect on the immunosuppressive activity. High levels of IL-6 were detected in TSN from all cases studied (n=5). When normal T cell were activated in TSN, a 100 fold further increase in IL-6 level was observed suggesting that this cytokine may be responsible for at least some of the observed effects of TSN. Antibody neutralization of the IL-6 in TSN demonstrated an increase in both Th1 cytokine production and CD40L expression. Furthermore, addition of recombinant IL-6 to T cells activated in media inhibited CD40L upregulation. In summary, B-CLL cells secrete factor(s) which inhibit T cell activation and proliferation and promote Th2 polarisation. These factors might contribute to the disease phenotype by impairing T cell responses to infection, predisposing to autoimmunity and promoting the growth of the malignant clone through the action of IL-6.

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