• Title/Summary/Keyword: Innate defense

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Targeting the Epithelium-Derived Innate Cytokines: From Bench to Bedside

  • Jongho Ham;Jae Woo Shin;Byeong Cheol Ko;Hye Young Kim
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.11.1-11.26
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    • 2022
  • When epithelial cells are exposed to potentially threatening external stimuli such as allergens, bacteria, viruses, and helminths, they instantly produce "alarmin" cytokines, namely, IL-33, IL-25, and TSLP. These alarmins alert the immune system about these threats, thereby mobilizing host immune defense mechanisms. Specifically, the alarmins strongly stimulate type-2 immune cells, including eosinophils, mast cells, dendritic cells, type-2 helper T cells, and type-2 innate lymphoid cells. Given that the alarm-raising role of IL-33, IL-25, and TSLP was first detected in allergic and infectious diseases, most studies on alarmins focus on their role in these diseases. However, recent studies suggest that alarmins also have a broad range of effector functions in other pathological conditions, including psoriasis, multiple sclerosis, and cancer. Therefore, this review provides an update on the epithelium-derived cytokines in both allergic and non-allergic diseases. We also review the progress of clinical trials on biological agents that target the alarmins and discuss the therapeutic potential of these agents in non-allergic diseases.

Sex hormones alter the response of Toll-like receptor 3 to its specific ligand in fallopian tube epithelial cells

  • Zandieh, Zahra;Amjadi, Fatemehsadat;Vakilian, Haghighat;Aflatoonian, Khashayar;Amirchaghmaghi, Elham;Fazeli, Alireza;Aflatoonian, Reza
    • Clinical and Experimental Reproductive Medicine
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    • v.45 no.4
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    • pp.154-162
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    • 2018
  • Objective: The fallopian tubes play a critical role in the early events of fertilization. The rapid innate immune defense is an important part of the fallopian tubes. Toll-like receptor 3 (TLR3), as a part of the innate immune system, plays an important role in detecting viral infections. In this basic and experimental study, the effect of sex hormones on the function of TLR3 in the OE-E6/E7 cell line was investigated. Methods: The functionality of TLR3 in this cell line was evaluated by cytokine measurements (interleukin [IL]-6 and IL-1b) and the effects of sex hormones on TLR3 were tested by an enzyme-linked immunosorbent assay kit. Additionally, TLR3 small interfering RNA (siRNA) and a TLR3 function-blocking antibody were used to confirm our findings. Results: The production of IL-6 significantly increased in the presence of polyinosinic-polycytidylic acid (poly(I:C)) as the TLR3 ligand. Using a TLR3-siRNA-ransfected OE-E6/E7 cell line and function-blocking antibody confirmed that cytokine production was due to TLR3. In addition, 17-${\beta}$ estradiol and progesterone suppressed the production of IL-6 in the presence and absence of poly(I:C). Conclusion: These results imply that sex hormones exerted a suppressive effect on the function of TLR3 in the fallopian tube cell line when different concentrations of sex hormones were present. The current results also suggest that estrogen receptor beta and nuclear progesterone receptor B are likely to mediate the hormonal regulation of TLR3, as these two receptors are the main estrogen and progesterone receptors in OEE6/E7 cell line.

Molecular Mechanisms of Generation for Nitric Oxide and Reactive Oxygen Species, and Role of the Radical Burst in Plant Immunity

  • Yoshioka, Hirofumi;Asai, Shuta;Yoshioka, Miki;Kobayashi, Michie
    • Molecules and Cells
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    • v.28 no.4
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    • pp.321-329
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    • 2009
  • Rapid production of nitric oxide (NO) and reactive oxygen species (ROS) has been implicated in the regulation of innate immunity in plants. A potato calcium-dependent protein kinase (StCDPK5) activates an NADPH oxidase StRBOHA to D by direct phosphorylation of N-terminal regions, and heterologous expression of StCDPK5 and StRBOHs in Nicotiana benthamiana results in oxidative burst. The transgenic potato plants that carry a constitutively active StCDPK5 driven by a pathogen-inducible promoter of the potato showed high resistance to late blight pathogen Phytophthora infestans accompanied by HR-like cell death and $H_2O_2$ accumulation in the attacked cells. In contrast, these plants showed high susceptibility to early blight necrotrophic pathogen Alternaria solani, suggesting that oxidative burst confers high resistance to biotrophic pathogen, but high susceptibility to necrotrophic pathogen. NO and ROS synergistically function in defense responses. Two MAPK cascades, MEK2-SIPK and cytokinesis-related MEK1-NTF6, are involved in the induction of NbRBOHB gene in N. benthamiana. On the other hand, NO burst is regulated by the MEK2-SIPK cascade. Conditional activation of SIPK in potato plants induces oxidative and NO bursts, and confers resistance to both biotrophic and necrotrophic pathogens, indicating the plants may have obtained during evolution the signaling pathway which regulates both NO and ROS production to adapt to wide-spectrum pathogens.

Design of INS/GNSS/TRN Integrated Navigation Considering Compensation of Barometer Error (기압고도계 오차 보상을 고려한 INS/GNSS/TRN 통합항법 설계)

  • Lee, Jungshin;Sung, Changky;Park, Byungsu;Lee, Hyungsub
    • Journal of the Korea Institute of Military Science and Technology
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    • v.22 no.2
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    • pp.197-206
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    • 2019
  • Safe aircraft requires highly reliable navigation information. The traditionally used inertial navigation system (INS) often displays faulty location information due to its innate errors. To overcome this, the INS/GNSS or INS/TRN integrated navigation can be used. However, GNSS is vulnerable to jamming and spoofing, while TRN can be degraded in the flat and repetitive terrains. In this paper, to improve the performance and ensure the high reliability of the navigation system, the INS/GNSS/TRN integrated navigation based on federated filter is designed. Master filter of the integrated navigation uses the estimates and covariances of two local filters - INS/GNSS and INS/TRN integrated filters. The local filters are designed with the EKF that is feedforward type and composed of the 17st state variables. And the INS/GNSS integrated navigation includes the barometer error compensation method. Finally, the proposed INS/GNSS/TRN integrated navigation is verified by vehicle and captive flight tests.

Expression and Purification of Toll-like Receptor 9 Cytoplasmic Domain in Pichia patoris (Pichia pastoris로부터 Toll-like Receptor 9의 세포 내 도메인 단백질의 발현과 순수분리 정제)

  • Lee Kyun-Young;Lee Kon-Ho
    • Journal of Plant Biotechnology
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    • v.32 no.4
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    • pp.269-273
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    • 2005
  • Toll-like receptors (TLR) are important components of innate immunity in the defense against pathogens. TLRs recognize pathogen-associated common molecular patterns. TLRs are similar to the receptors involved in defense responses in plants. TLR protein is a type 1 membrane protein, consisting of an extracellular domain containing leucine-rich repeats and a cytoplasmic domain. The cytoplasmic domain delivers ligand recognition signals that result in production of anti-microbial agents. The cytoplasmic domain (amino acid 858-1032) of toll-like receptor 9 has been expressed using methylotrophic yeast Pichia pastoris. The protein expression was confirmed by Western-blot, N-terminal sequencing and MALDl-TOF mass spectrometry. The proteins have been purified by nickel affinity, cation exchange and gel-filtration chromatography.

Autophagy in neutrophils

  • Shrestha, Sanjeeb;Lee, Jae Man;Hong, Chang-Won
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.1
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    • pp.1-10
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    • 2020
  • Autophagy is a highly conserved intracellular degradation and energy-recycling mechanism that contributes to the maintenance of cellular homeostasis. Extensive researches over the past decades have defined the role of autophagy innate immune cells. In this review, we describe the current state of knowledge regarding the role of autophagy in neutrophil biology and a picture of molecular mechanism underlying autophagy in neutrophils. Neutrophils are professional phagocytes that comprise the first line of defense against pathogen. Autophagy machineries are highly conserved in neutrophils. Autophagy is not only involved in generalized function of neutrophils such as differentiation in bone marrow but also plays crucial role effector functions of neutrophils such as granule formation, degranulation, neutrophil extracellular traps release, cytokine production, bactericidal activity and controlling inflammation. This review outlines the current understanding of autophagy in neutrophils and provides insight towards identification of novel therapeutics targeting autophagy in neutrophils.

Beyond Viral Interferon Regulatory Factors: Immune Evasion Strategies

  • Myoung, Jinjong;Lee, Shin-Ae;Lee, Hye-Ra
    • Journal of Microbiology and Biotechnology
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    • v.29 no.12
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    • pp.1873-1881
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    • 2019
  • The innate immune response serves as a first-line-of-defense mechanism for a host against viral infection. Viruses must therefore subvert this anti-viral response in order to establish an efficient life cycle. In line with this fact, Kaposi's sarcoma-associated herpesvirus (KSHV) encodes numerous genes that function as immunomodulatory proteins to antagonize the host immune system. One such mechanism through which KSHV evades the host immunity is by encoding a viral homolog of cellular interferon (IFN) regulatory factors (IRFs), known as vIRFs. Herein, we summarize recent advances in the study of the immunomodulatory strategies of KSHV vIRFs and their effects on KSHV-associated pathogenesis.

Streptococcus mutans Strains Isolated in Korea Can Hardly Metabolize Exogenous Nitric Oxide

  • Lee, Hwa Jeong;Bang, Iel Soo
    • International Journal of Oral Biology
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    • v.40 no.4
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    • pp.217-221
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    • 2015
  • Cariogenic Streptococcus mutans encounters a variety of host defense factors produced in oral cavity. Nitric oxide (NO) and NO-mediated reactive nitrogen species are potential antimicrobials of innate immunity that can threaten the fitness of S. mutans in their ecological niches. Streptococcal strategies to detoxify cytotoxic NO, which allow S. mutans to persist in caries or other environments of the oral cavity, remain unknown. In this study, we directly measured NO consumption rates of S. mutans isolated in Korea. Surprisingly, all S. mutans strains were unable to consume exogenous NO efficiently, while an intracellular parasite Salmonella enterica serovar Typhimurium expressing the NO-metabolizing enzyme flavohemoglobin consumed most of the NO. This result suggested that S. mutans has alternative detoxification systems for tolerating NO-induced nitrosative stresses.

Regulation of Nrf2-Mediated Phase II Detoxification and Anti-oxidant Genes

  • Keum, Young-Sam
    • Biomolecules & Therapeutics
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    • v.20 no.2
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    • pp.144-151
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    • 2012
  • The molecular mechanisms by which a variety of naturally-occurring dietary compounds exert chemopreventive effects have been a subject of intense scientific investigations. Induction of phase II detoxification and anti-oxidant enzymes through activation of Nrf2/ARE-dependent gene is recognized as one of the major cellular defense mechanisms against oxidative or xenobiotic stresses and currently represents a critical chemopreventive mechanism of action. In the present review, the functional significance of Keap1/Nrf2 protein module in regulating ARE-dependent phase II detoxification and anti-oxidant gene expression is discussed. The biochemical mechanisms underlying the phosphorylation and expression of Keap1/Nrf2 proteins that are controlled by the intracellular signaling kinases and ubiquitin-mediated E3 ligase system as well as control of nucleocytoplasmic translocation of Nrf2 by its innate nuclear export signal (NES) are described.

Signaling Pathways Controlling Microglia Chemotaxis

  • Fan, Yang;Xie, Lirui;Chung, Chang Y.
    • Molecules and Cells
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    • v.40 no.3
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    • pp.163-168
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    • 2017
  • Microglia are the primary resident immune cells of the central nervous system (CNS). They are the first line of defense of the brain's innate immune response against infection, injury, and diseases. Microglia respond to extracellular signals and engulf unwanted neuronal debris by phagocytosis, thereby maintaining normal cellular homeostasis in the CNS. Pathological stimuli such as neuronal injury induce transformation and activation of resting microglia with ramified morphology into a motile amoeboid form and activated microglia chemotax toward lesion site. This review outlines the current research on microglial activation and chemotaxis.