• Title/Summary/Keyword: Immune mechanism

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Differential Gene Expression Profiling in Human Promyelocytic Leukemia Cells Treated with Benzene and Ethylbenzene

  • Sarma, Sailendra Nath;Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.4 no.4
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    • pp.267-277
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    • 2008
  • Benzene and ethylbenzene (BE), the volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Chronic exposure of benzene is responsible for myeloid leukemia and also ethylbenzene is also recognized as a possible carcinogen. To evaluate the BE effect on human, whole human genome 35 K oligonucleotide microarray were screened for the identification of the differential expression profiling. We identified 280 up-regulated and 201 down-regulated genes changed by more than 1.5 fold by BE exposure. Functional analysis was carried out by using DAVID bioinformatics software. Clustering of these differentially expressed genes were associated with immune response, cytokine-cytokine receptor interaction, toll-like signaling pathway, small cell lung cancer, immune response, apoptosis, p53 signaling pathway and MAPKKK cascade possibly constituting alternative or subordinate pathways of hematotoxicity and immune toxicity. Gene ontology analysis methods including biological process, cellular components, molecular function and KEGG pathway thus provide a fundamental basis of the molecular pathways through BEs exposure in human lymphoma cells. This may provides a valuable information to do further analysis to explore the mechanism of BE induced hematotoxicity.

The emerging role of myeloid-derived suppressor cells in radiotherapy

  • Kang, Changhee;Jeong, Seong-Yun;Song, Si Yeol;Choi, Eun Kyung
    • Radiation Oncology Journal
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    • v.38 no.1
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    • pp.1-10
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    • 2020
  • Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.

Increase in Hypotonic Stress-Induced Endocytic Activity in Macrophages via ClC-3

  • Yan, Yutao;Ding, Yu;Ming, Bingxia;Du, Wenjiao;Kong, Xiaoling;Tian, Li;Zheng, Fang;Fang, Min;Tan, Zheng;Gong, Feili
    • Molecules and Cells
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    • v.37 no.5
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    • pp.418-425
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    • 2014
  • Extracellular hypotonic stress can affect cellular function. Whether and how hypotonicity affects immune cell function remains to be elucidated. Macrophages are immune cells that play key roles in adaptive and innate in immune reactions. The purpose of this study was to investigate the role and underlying mechanism of hypotonic stress in the function of bone marrow-derived macrophages (BMDMs). Hypotonic stress increased endocytic activity in BMDMs, but there was no significant change in the expression of CD80, CD86, and MHC class II molecules, nor in the secretion of TNF-${\alpha}$ or IL-10 by BMDMs. Furthermore, the enhanced endocytic activity of BMDMs triggered by hypotonic stress was significantly inhibited by chloride channel-3 (ClC-3) siRNA. Our findings suggest that hypotonic stress can induce endocytosis in BMDMs and that ClC-3 plays a central role in the endocytic process.

A controller Design using Immune Feedback Mechanism (인체 면역 피드백 메카니즘을 활용한 제어기 설계)

  • Park, Jin-Hyun;Kim, Hyun-Duck;Choi, Young-Kiu
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • v.9 no.2
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    • pp.701-704
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    • 2005
  • PID controllers, which have been widely used in industry, have a simple structure and robustness to modeling error. But They are difficult to have uniformly good control performance in system parameters variation or different velocity command. In this paper, we propose a nonlinear adaptive PID controller based on a cell-mediated immune response and a gradient descent learning. This algorithm has a simple structure and robustness to system parameters variation. To verify performances of the proposed nonlinear adaptive PID controller, the speed control of nonlinear DC motor is performed. The simulation results show that the proposed control systems are effective in tracking a command velocity under system parameters variation.

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Study of Danger-Theory-Based Intrusion Detection Technology in Virtual Machines of Cloud Computing Environment

  • Zhang, Ruirui;Xiao, Xin
    • Journal of Information Processing Systems
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    • v.14 no.1
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    • pp.239-251
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    • 2018
  • In existing cloud services, information security and privacy concerns have been worried, and have become one of the major factors that hinder the popularization and promotion of cloud computing. As the cloud computing infrastructure, the security of virtual machine systems is very important. This paper presents an immune-inspired intrusion detection model in virtual machines of cloud computing environment, denoted I-VMIDS, to ensure the safety of user-level applications in client virtual machines. The model extracts system call sequences of programs, abstracts them into antigens, fuses environmental information of client virtual machines into danger signals, and implements intrusion detection by immune mechanisms. The model is capable of detecting attacks on processes which are statically tampered, and is able to detect attacks on processes which are dynamically running. Therefore, the model supports high real time. During the detection process, the model introduces information monitoring mechanism to supervise intrusion detection program, which ensures the authenticity of the test data. Experimental results show that the model does not bring much spending to the virtual machine system, and achieves good detection performance. It is feasible to apply I-VMIDS to the cloud computing platform.

Evaluation of Hypersensitivity Reaction to Dental Materials with a Patch Test (첩포시험을 이용한 치과용 재료의 알러지 평가)

  • Jeon, Hee-Sun;Park, June-Sang;Ko, Myung-Yun
    • Journal of Oral Medicine and Pain
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    • v.25 no.2
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    • pp.167-172
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    • 2000
  • Both immune reaction and hypersensitivity reaction are occurred by the same mechanism, the antigen and antibody reaction. The favorable result of this reaction towards a host is called clinically an immune reaction and the opposite results is called an hypersensitivity reaction. Type IV hypersensitivity reaction is a delayed type which is related to the cellular immune reaction and a contact hypersensitivity is included in this type. Various dental materials such as metal (mercury, nickel, chrome, cobalt), resin and eugenol are etiologic substances. Patch test kit is composed of test substance with a controlled concentration which respond only to a susceptible patient and an aluminum chamber, and etiologic substances for hypersensitivity can be easily and comfortably found just by applying the kit to the patient's skin. In this case report, the patch test was performed to a patients with oral lichen planus and the allergen, restorative material was found. After removal of the matching restoration from the patient's mouth, the symptom was improved.

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MiT Family Transcriptional Factors in Immune Cell Functions

  • Kim, Seongryong;Song, Hyun-Sup;Yu, Jihyun;Kim, You-Me
    • Molecules and Cells
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    • v.44 no.5
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    • pp.342-355
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    • 2021
  • The microphthalmia-associated transcription factor family (MiT family) proteins are evolutionarily conserved transcription factors that perform many essential biological functions. In mammals, the MiT family consists of MITF (microphthalmia-associated transcription factor or melanocyte-inducing transcription factor), TFEB (transcription factor EB), TFE3 (transcription factor E3), and TFEC (transcription factor EC). These transcriptional factors belong to the basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. The best studied functions of MiT proteins include lysosome biogenesis and autophagy induction. In addition, they modulate cellular metabolism, mitochondria dynamics, and various stress responses. The control of nuclear localization via phosphorylation and dephosphorylation serves as the primary regulatory mechanism for MiT family proteins, and several kinases and phosphatases have been identified to directly determine the transcriptional activities of MiT proteins. In different immune cell types, each MiT family member is shown to play distinct or redundant roles and we expect that there is far more to learn about their functions and regulatory mechanisms in host defense and inflammatory responses.

Anti-Inflammatory Role of TAM Family of Receptor Tyrosine Kinases Via Modulating Macrophage Function

  • Lee, Chang-Hee;Chun, Taehoon
    • Molecules and Cells
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    • v.42 no.1
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    • pp.1-7
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    • 2019
  • Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.

Nonstructural Protein of Severe Fever with Thrombocytopenia Syndrome Phlebovirus Inhibits TBK1 to Evade Interferon-Mediated Response

  • Lee, Jae Kyung;Shin, Ok Sarah
    • Journal of Microbiology and Biotechnology
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    • v.31 no.2
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    • pp.226-232
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    • 2021
  • Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging phlebovirus of the Phenuiviridae family that has been circulating in the following Asian countries: Vietnam, Myanmar, Taiwan, China, Japan, and South Korea. Despite the increasing infection rates and relatively high mortality rate, there is limited information available regarding SFTSV pathogenesis. In addition, there are currently no vaccines or effective antiviral treatments available. Previous reports have shown that SFTSV suppresses the host immune response and its nonstructural proteins (NSs) function as an antagonist of type I interferon (IFN), whose induction is an essential part of the host defense system against viral infections. Given that SFTSV NSs suppress the innate immune response by inhibiting type I IFN, we investigated the mechanism utilized by SFTSV NSs to evade IFNmediated response. Our co-immunoprecipitation data suggest the interactions between NSs and retinoic acid inducible gene-I (RIG-I) or TANK binding kinase 1 (TBK1). Furthermore, confocal analysis indicates the ability of NSs to sequester RIG-I and related downstream molecules in the cytoplasmic structures called inclusion bodies (IBs). NSs are also capable of inhibiting TBK1-interferon regulatory factor 3 (IRF3) interaction, and therefore prevent the phosphorylation and nuclear translocation of IRF3 for the induction of type I IFN. The ability of SFTSV NSs to interact with and sequester TBK1 and IRF3 in IBs demonstrate an effective yet unique method utilized by SFTSV to evade and suppress host immunity.

Emerging role of bystander T cell activation in autoimmune diseases

  • Shim, Chae-Hyeon;Cho, Sookyung;Shin, Young-Mi;Choi, Je-Min
    • BMB Reports
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    • v.55 no.2
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    • pp.57-64
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    • 2022
  • Autoimmune disease is known to be caused by unregulated self-antigen-specific T cells, causing tissue damage. Although antigen specificity is an important mechanism of the adaptive immune system, antigen non-related T cells have been found in the inflamed tissues in various conditions. Bystander T cell activation refers to the activation of T cells without antigen recognition. During an immune response to a pathogen, bystander activation of self-reactive T cells via inflammatory mediators such as cytokines can trigger autoimmune diseases. Other antigen-specific T cells can also be bystander-activated to induce innate immune response resulting in autoimmune disease pathogenesis along with self-antigen-specific T cells. In this review, we summarize previous studies investigating bystander activation of various T cell types (NKT, γδ T cells, MAIT cells, conventional CD4+, and CD8+ T cells) and discuss the role of innate-like T cell response in autoimmune diseases. In addition, we also review previous findings of bystander T cell function in infection and cancer. A better understanding of bystander-activated T cells versus antigen-stimulated T cells provides a novel insight to control autoimmune disease pathogenesis.