scholarly journals Defensins and Sepsis

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Guo-Hao Xie ◽  
Qi-Xing Chen ◽  
Bao-Li Cheng ◽  
Xiang-Ming Fang
Keyword(s):  
Dendritic Cells ◽  
Critical Illness ◽  
Inflammatory Diseases ◽  
Genetic Studies ◽  
Innate And Adaptive Immunity ◽  
Mortality And Morbidity ◽  
Disulphide Bonds ◽  
Inflammatory Processes

Sepsis is a leading cause of mortality and morbidity in the critical illness. Multiple immune inflammatory processes take part in the pathogenesis of sepsis. Defensins are endogenous antimicrobial peptides with three disulphide bonds created by six cysteine residues. Besides the intrinsic microbicidal properties, defensins are active players which modulate both innate and adaptive immunity against various infections. Defensins can recruit neutrophils, enhance phagocytosis, chemoattract T cells and dendritic cells, promote complement activation, and induce IL-1βproduction and pyrotosis. Previous publications have documented that defensins play important roles in a series of immune inflammatory diseases including sepsis. This review aims to briefly summarize in vitro, in vivo, and genetic studies on defensins’ effects as well as corresponding mechanisms within sepsis and highlights their promising findings which may be potential targets in future therapies of sepsis.

scholarly journals Dendritic Cells under Hypoxia: How Oxygen Shortage Affects the Linkage between Innate and Adaptive Immunity

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Sandra Winning ◽  
Joachim Fandrey
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Mature Dendritic Cell ◽  
Innate And Adaptive Immunity ◽  
Cell Functions ◽  
Adaptive Immune ◽  
Oxygen Shortage

Dendritic cells (DCs) are considered as one of the main regulators of immune responses. They collect antigens, process them, and present typical antigenic structures to lymphocytes, thereby inducing an adaptive immune response. All these processes take place under conditions of oxygen shortage (hypoxia) which is often not considered in experimental settings. This review highlights how deeply hypoxia modulates human as well as mouse immature and mature dendritic cell functions. It tries to linkin vitroresults to actualin vivostudies and outlines how hypoxia-mediated shaping of dendritic cells affects the activation of (innate) immunity.

scholarly journals Genetically ModifiedLactococcus lactisfor Delivery of Human Interleukin-10 to Dendritic Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Inge L. Huibregtse ◽  
Sebatian A. Zaat ◽  
Martien L. Kapsenberg ◽  
Maria A. Sartori da Silva ◽  
Maikel P. Peppelenbosch ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Inflammatory Diseases ◽  
Cell Interaction ◽  
Interleukin 10 ◽  
Suppressive Effect ◽  
Th Cells ◽  
Enhanced Production ◽  
Th Cell

Interleukin-10 (IL-10) plays an indispensable role in mucosal tolerance by programming dendritic cells (DCs) to induce suppressor Th-cells. We have tested the modulating effect ofL. lactissecreting human IL-10 (L.  lactisIL-10) on DC function in vitro. Monocyte-derived DC incubated withL.  lactisIL-10induced effector Th-cells that markedly suppressed the proliferation of allogenic Th-cells as compared toL. lactis. This suppressive effect was only seen when DC showed increased CD83 and CD86 expression. Furthermore, enhanced production of IL-10 was measured in bothL.  lactisIL-10-derived DC and Th-cells compared toL. lactis-derived DC and Th-cells. Neutralizing IL-10 during DC-Th-cell interaction and coculturingL.  lactisIL-10-derived suppressor Th-cells with allogenic Th-cells in a transwell system prevented the induction of suppressor Th-cells. Only 130 pg/mL of bacterial-derived IL-10 and 40 times more exogenously added recombinant human IL-10 were needed during DC priming for the generation of suppressor Th-cells. The spatially restricted delivery of IL-10 by food-grade bacteria is a promising strategy to induce suppressor Th-cellsin vivoand to treat inflammatory diseases.

scholarly journals Targeting of microRNA-142-3p in dendritic cells regulates endotoxin-induced mortality

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6172-6183 ◽  
Author(s):  
Yaping Sun ◽  
Sooryanarayana Varambally ◽  
Christopher A. Maher ◽  
Qi Cao ◽  
Peter Chockley ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Critical Role ◽  
Locked Nucleic Acid ◽  
Phosphorothioate Oligonucleotide ◽  
Unbiased Manner ◽  
Inflammatory Processes ◽  
Novel Strategy ◽  
Luciferase Reporters

Abstract While miRNAs are increasingly linked to various immune responses, whether they can be targeted for regulating in vivo inflammatory processes such as endotoxin-induced Gram-negative sepsis is not known. Production of cytokines by the dendritic cells (DCs) plays a critical role in response to endotoxin, lipopolysaccharide (LPS). We profiled the miRNA and mRNA of CD11c+ DCs in an unbiased manner and found that at baseline, miR-142-3p was among the most highly expressed endogenous miRs while IL-6 was among the most highly expressed mRNA after LPS stimulation. Multiple computational algorithms predicted the IL-6 3′ untranslated region (UTR) to be a target of miR-142-3p. Studies using luciferase reporters carrying wild-type (WT) and mutant IL-6 3′UTR confirmed IL-6 as a target for miR-142-3p. In vitro knockdown and overexpression studies demonstrated a critical and specific role for miR142-3p in regulating IL-6 production by the DCs after LPS stimulation. Importantly, treatment of only WT but not the IL-6–deficient (IL-6−/−) mice with locked nucleic acid (LNA)–modified phosphorothioate oligonucleotide complementary to miR 142-3p reduced endotoxin-induced mortality. These results demonstrate a critical role for miR-142-3p in regulating DC responses to LPS and provide proof of concept for targeting miRs as a novel strategy for treatment of endotoxin-induced mortality.

scholarly journals Organ-derived dendritic cells have differential effects on alloreactive T cells

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2929-2940 ◽  
Author(s):  
Theo D. Kim ◽  
Theis H. Terwey ◽  
Johannes L. Zakrzewski ◽  
David Suh ◽  
Adam A. Kochman ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
Mortality And Morbidity ◽  
Alloreactive T Cells ◽  
Target Organs ◽  
Peripheral Lymph ◽  
Stimulatory Capacity

Dendritic cells (DCs) are considered critical for the induction of graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In addition to their priming function, dendritic cells have been shown to induce organ-tropism through induction of specific homing molecules on T cells. Using adoptive transfer of CFSE-labeled cells, we first demonstrated that alloreactive T cells differentially up-regulate specific homing molecules in vivo. Host-type dendritic cells from the GVHD target organs liver and spleen or skin- and gut-draining lymph nodes effectively primed naive allogeneic T cells in vitro with the exception of liver-derived dendritic cells, which showed less stimulatory capacity. Gut-derived dendritic cells induced alloreactive donor T cells with a gut-homing phenotype that caused increased GVHD mortality and morbidity compared with T cells stimulated with dendritic cells from spleen, liver, and peripheral lymph nodes in an MHC-mismatched murine BMT model. However, in vivo analysis demonstrated that the in vitro imprinting of homing molecules on alloreactive T cells was only transient. In conclusion, organ-derived dendritic cells can efficiently induce specific homing molecules on alloreactive T cells. A gut-homing phenotype correlates with increased GVHD mortality and morbidity after murine BMT, underlining the importance of the gut in the pathophysiology of GVHD.

scholarly journals Therapeutic normal IgG intravenous immunoglobulin activates Wnt-β-catenin pathway in dendritic cells

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Anupama Karnam ◽  
Naresh Rambabu ◽  
Mrinmoy Das ◽  
Melissa Bou-Jaoudeh ◽  
Sandrine Delignat ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Intravenous Immunoglobulin ◽  
Inflammatory Diseases ◽  
Central Component ◽  
Independent Manner ◽  
Reciprocal Regulation ◽  
Autoimmune And Inflammatory Diseases ◽  
Anti Inflammatory

AbstractTherapeutic normal IgG intravenous immunoglobulin (IVIG) is a well-established first-line immunotherapy for many autoimmune and inflammatory diseases. Though several mechanisms have been proposed for the anti-inflammatory actions of IVIG, associated signaling pathways are not well studied. As β-catenin, the central component of the canonical Wnt pathway, plays an important role in imparting tolerogenic properties to dendritic cells (DCs) and in reducing inflammation, we explored whether IVIG induces the β-catenin pathway to exert anti-inflammatory effects. We show that IVIG in an IgG-sialylation independent manner activates β-catenin in human DCs along with upregulation of Wnt5a secretion. Mechanistically, β-catenin activation by IVIG requires intact IgG and LRP5/6 co-receptors, but FcγRIIA and Syk are not implicated. Despite induction of β-catenin, this pathway is dispensable for anti-inflammatory actions of IVIG in vitro and for mediating the protection against experimental autoimmune encephalomyelitis in vivo in mice, and reciprocal regulation of effector Th17/Th1 and regulatory T cells.

scholarly journals Expression of cell adhesion molecules, chemokines and chemokine receptors involved in leukocyte traffic in rats undergoing autoimmune orchitis

Reproduction ◽  
2012 ◽  
Vol 143 (5) ◽  
pp. 651-662 ◽  
Author(s):  
V A Guazzone ◽  
P Jacobo ◽  
B Denduchis ◽  
L Lustig
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Chemokine Receptors ◽  
Inflammatory Diseases ◽  
Autoimmune Attack ◽  
Inflammatory Processes ◽  
Autoimmune Orchitis

The testis is considered an immunologically privileged site where germ cell antigens are protected from autoimmune attack. Yet in response to infections, inflammatory diseases, or trauma, there is an influx of leukocytes to testicular interstitium. Interactions between endothelial cells (EC) and circulating leukocytes are implicated in the initiation and evolution of inflammatory processes. Chemokines are a family of chemoattractant cytokines characterized by their ability to both recruit and activate cells. Thus, we investigated the expression of CCL3, its receptors, and adhesion molecules CD31 and CD106 in an in vivo model of experimental autoimmune orchitis (EAO). In EAO, the highest content of CCL3 in testicular fluid coincides with onset of the disease. However, CCL3 released in vitro by testicular macrophages is higher during the immunization period. The specific chemokine receptors, CCR1 and CCR5, were expressed by testicular monocytes/macrophages and an increased number of CCR5+ cells was associated with the degree of testicular lesion. EC also play an essential role by facilitating leukocyte recruitment via their ability to express cell surface adhesion molecules that mediate interactions with leukocytes in the bloodstream. Rats with EAO showed a significant increase in the percentage of CD31+ EC that upregulate the expression of CD106. The percentage of leukocytes isolated from peripheral blood and lymph nodes expressing CD49d (CD106 ligand) also increases during orchitis. These data suggest that cell adhesion molecules, in conjunction with chemokines, contribute to the formation of a chemotactic gradient within the testis, causing the leukocyte infiltration characteristic of EAO histopathology.

scholarly journals PPARγ in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation

2017 ◽  
Vol 214 (10) ◽  
pp. 3015-3035 ◽  
Author(s):  
Samuel Philip Nobs ◽  
Sara Natali ◽  
Lea Pohlmeier ◽  
Katarzyna Okreglicka ◽  
Christoph Schneider ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Inflammatory Diseases ◽  
Th2 Cells ◽  
M2 Macrophage ◽  
Airway Responses

Type-2 immune responses are well-established drivers of chronic inflammatory diseases, such as asthma, and represent a large burden on public health systems. The transcription factor PPARγ is known to promote M2-macrophage and alveolar macrophage development. Here, we report that PPARγ plays a key role in both T cells and dendritic cells (DCs) for development of type-2 immune responses. It is predominantly expressed in mouse Th2 cells in vitro and in vivo as well as human Th2 cells from allergic patients. Using conditional knockouts, we show that PPARγ signaling in T cells, although largely dispensable for IL-4 induction, is critical for IL-33–driven Th2 effector function in type-2 allergic airway responses. Furthermore, we demonstrate that IL-4 and IL-33 promote up-regulation of PPARγ in lung-resident CD11b+ DCs, which enhances migration to draining lymph nodes and Th2 priming capacity. Thus, we uncover a surprising proinflammatory role for PPARγ and establish it as a novel, important mediator of DC–T cell interactions in type-2 immunity.

Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Cellular Level ◽  
Antiinflammatory Drugs ◽  
Suitable Alternative ◽  
Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

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