• IMMUNE NETWORK
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• 제23권5호
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• pp.40.1-40.14
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• 2023

Glucocorticoids suppress the vascular inflammation that occurs under hypercholesterolemia, as demonstrated in an animal model fed a high-cholesterol diet. However, the molecular mechanisms underlying these beneficial effects remain poorly understood. Because cholesterol is oxidized to form cholesterol oxides (oxysterols) that are capable of inducing inflammation, we investigated whether glucocorticoids affect the immune responses evoked by 7α-hydroxycholesterol (7αOHChol). The treatment of human THP-1 monocytic cells with dexamethasone (Dex) and prednisolone (Pdn) downregulated the expression of pattern recognition receptors (PRRs), such as TLR6 and CD14, and diminished 7αOHChol-enhanced response to FSL-1, a TLR2/6 ligand, and lipopolysaccharide, which interacts with CD14 to initiate immune responses, as determined by the reduced secretion of IL-23 and CCL2, respectively. Glucocorticoids weakened the 7αOHChol-induced production of CCL2 and CCR5 ligands, which was accompanied by decreased migration of monocytic cells and CCR5-expressing Jurkat T cells. Treatment with Dex or Pdn also reduced the phosphorylation of the Akt-1 Src, ERK1/2, and p65 subunits. These results indicate that both Dex and Pdn impair the expression of PRRs and their downstream products, chemokine production, and phosphorylation of signaling molecules. Collectively, glucocorticoids suppress the innate immune response and activation of monocytic cells to an inflammatory phenotype enhanced or induced by 7αOHChol, which may contribute to the anti-inflammatory effects in hypercholesterolemic conditions.

• 한국어병학회지
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• 제26권3호
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• pp.255-263
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• 2013

선천성 면역반응은 감염성 질병에 대한 저항력이 부족한 초기 발달단계의 자치어에게 중요하다. 특히 lectin은 선천성 면역반응에 많은 기여를 하고 있으며 종류 또한 다양하다. Lectin의 종류 중 하나인 galectin은 어류 점액 내에 존재하며 선천적으로 외부 병원체로부터 숙주를 보호하는 기능을 지니고 있다. 하지만 어류 galectin과 초기발생단계 시기와 관련된 연구들은 부족한 실정이다. 본 연구는 넙치에서 발현되는 galecin-1을 통하여 자치어의 초기발생단계별 그리고 성어의 조직별 발현을 조사하였다. 초기발생단계별 galectin 발현을 조사한 결과, 부화 전 수정란의 낭배기부터 galectin-1 유전자의 발현이 시작되었으며, 부화 후 25일까지 서서히 증가하였다. 부화 후 30~35일에 galectin-1 유전자의 발현량이 급격하게 증가하였고, 그 이후의 galecin-1 유전자의 발현량은 서서히 감소하였다. 성어 (5개월령, 29개월령)의 조직별 galectin 발현을 조사한 결과, 근육, 장, 지느러미, 위, 눈 조직 순서로 높게 발현하였고, 이외의 조직에서는 발현이 나타나지 않았다. 초기발생단계에서 galectin-1의 발현이 증가되는 것은 낭배기부터 넙치의 근육, 지느러미 그리고 눈 조직이 형성되고 galectin의 분비가 시작되어 기능을 나타내기 때문인 것으로 추측된다. 부화 후 30일부터 galectin의 발현량이 많이 증가하는 것은 장과 위 조직이 활성화됨에 따라 점액의 분비량이 증가하여 galectin의 발현량 또한 증가하는 것으로 판단된다. 이로써 넙치 초기발생단계 시기의 galectin-1 유전자의 발현패턴과 galectin이 점액 내에 다량 포함되어 있는 것을 확인하였으며, galectin의 발현은 선천적 면역반응으로 넙치의 초기발생단계 시기와 성어기에 중요할 것으로 판단된다.

• 한국환경보건학회지
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• 제40권4호
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• pp.265-278
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• 2014

Microbes such as bacteria, fungi, archaea, protists, and viruses are ubiquitous and people are exposed to them continuously. Endotoxin is a component of the outer membrane of Gram-negative bacteria and a potent proinflammaotry substance. When a person is exposed to environmental endotoxin, an innate immune response is initiated upon the initial recognition and this response produces various inflammatory mediators and recruits inflammatory cells to the exposed tissues. A purified chemical form of endotoxin is called lipopolysaccharide (LPS), and the lipid A portion of the molecule is a biologically active moiety. Exposure to endotoxin may result in various complex health effects depending on time, route, and dose of exposure, as well as host susceptibility. Gene-environment interactions play important roles in health effects of endotoxin exposure, e.g. development or aggravation of asthma. To accurately assess exposure to endotoxin in environmental or epidemiologic studies, methods of sampling, extraction, and analysis must be carefully selected since the selected methods may substantially affect analytical results and there is no internationally-agreed standard method to date. The lack of a standardized method hampers the establishment of exposure-response relationships. While an internationally-agreed health-based exposure limit does not exist, the Dutch Expert Committee on Occupational Safety recently recommended $90EU/m^3$ as a health-based occupational exposure limit. The current article reviews various scientific issues on how we measure environmental endotoxin and the health effects of endotoxin exposure.

• BMB Reports
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• 제51권5호
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• pp.219-224
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• 2018

Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to tumor necrosis factor alpha. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore, necroptotic cell death plays both physiological and pathological roles. Physiologically, necroptosis induce an innate immune response as well as premature assembly of viral particles in cells infected with virus that abrogates host apoptotic machinery. On the other hand, necroptosis per se is detrimental, causing various diseases such as sepsis, neurodegenerative diseases and ischemic reperfusion injury. This review discusses the signaling pathways leading to necroptosis, associated necroptotic proteins with target-specific inhibitors and diseases involved. Several studies currently focus on protective approaches to inhibiting necroptotic cell death. In cancer biology, however, anticancer drug resistance severely hampers the efficacy of chemotherapy based on apoptosis. Pharmacological switch of cell death finds therapeutic application in drug- resistant cancers. Therefore, the possible clinical role of necroptosis in cancer control will be discussed in brief.

• Journal of Microbiology and Biotechnology
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• 제29권12호
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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.

• 한국가금학회지
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• 제35권3호
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• pp.225-240
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• 2008

Marek's disease virus(MDV) is a highly cell-associated, lymphotropic $\alpha$-herpesvirus that causes paralysis and neoplastic disease in chickens. The disease has been controlled by vaccination which was provided the first evidence for a malignant cancer being controlled by an antiviral vaccine. Marek's disease pathogenesis is complex, involving cytolytic and latent infection of lymphoid cells and oncogenic transformation of $CD4^+$ T cells in susceptible chickens. MDV targets a number of different cell types during its life cycle. Lymphocytes play an essential role, although within them virus production is restricted and only virion are produced. Innate and adaptive immune responses develop in response to infection, but infection of lymphocytes results in immunosuppressive effects. Hence in MDV-infected birds, MDV makes its host more vulnerable to tumour development as well as to other pathogens. All chickens are susceptible to MDV infection, and vaccination is essential to protect the susceptible host from developing clinical disease. Nevertheless, MDV infects and replicates in vaccinated chickens, with the challenge virus being shed from the feather-follicle epithelium. The outcome of infection with MDV depends on a complex interplay of factors involving the MDV pathotype and the host genotype. Host factors that influence the course of MD are predominantly the responses of the innate and adaptive immune systems, and these are modulated by: age at infection and maturity of the immune system; vaccination status; the sex of the host; and various physiological factors.

• KSBB Journal
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• 제25권6호
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• pp.497-506
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• 2010

Vaccine is a protective clinical measure capable of persuading immune system against infectious agents. Vaccine can be categorized as live attenuated and inactivated. Live attenuated vaccines activate immunity similar to natural infection by replicating living organisms whereas inactivated vaccines are either whole cell vaccines, eliciting immune response by killed organisms,or subunit vaccines, stimulating immunity by non-replicating sub cellular parts. The components of vaccine play a critical role in deciding the immune response mediated by the vaccine. The innate immune responds against the antigen component. Adjuvants represent an importantcomponent of vaccine for enhancing the immunogenicity of the antigens. Subunit vaccines with isolated fractions of killed and recombinant antigens are mostly co-administered with adjuvants. The delivery system of the vaccine is another essential component to ensurethat vaccine is delivered to the right target with right dosage form. Furthermore, vaccine delivery system ensures that the desired immune response is achieved by manipulating the optimal interaction of vaccine and adjuvantwith the immune cell. The aforementioned components along with routes of administration of vaccine are the key elements of a successful vaccination procedure. Vaccines can be administered either orally or by parenteral routes. Many groups had made remarkable efforts for the development of new vaccine and delivery system. The emergence of new vaccine delivery system may lead to pursue the immunization goals with better clinical practices.

• International Journal of Oral Biology
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• 제42권3호
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• pp.85-90
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• 2017

Mitochondria participate in various intracellular metabolic pathways such as generating intracellular ATP, synthesizing several essential molecules, regulating calcium homeostasis, and producing the cell's reactive oxygen species (ROS). Emerging studies have demonstrated newly discovered roles of mitochondria, which participate in the regulation of innate immune responses by modulating NLRP3 inflammasomes. Here, we review the recently proposed pathways to be involved in mitochondria-mediated regulation of inflammasome activation and inflammation: 1) mitochondrial ROS, 2) calcium mobilization, 3) nicotinamide adenine dinucleotide ($NAD^+$) reduction, 4) cardiolipin, 5) mitofusin, 6) mitochondrial DNA, 7) mitochondrial antiviral signaling protein. Furthermore, we highlight the significance of mitophagy as a negative regulator of mitochondrial damage and NLRP3 inflammasome activation, as potentially helpful therapeutic approaches which could potentially address uncontrolled inflammation.

• Journal of Microbiology and Biotechnology
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• 제29권10호
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• pp.1506-1521
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• 2019

Tuberculosis, which is caused by Mycobacterium tuberculosis (Mtb), is among the most pressing worldwide problems. Mtb uniquely interacts with innate immune cells through various pattern recognition receptors. These interactions initiate several inflammatory pathways that play essential roles in controlling Mtb pathogenesis. Although the TLR signaling pathways have essential roles in numerous host's immune defense responses, the role of TLR signaling in the response to Mtb infection is still unclear. This review presents discussions on host-Mtb interactions in terms of Mtb-mediated TLR signaling. In addition, we highlight recent discoveries pertaining to these pathways that may help in new immunotherapeutic opportunities.

• 대한약학회:학술대회논문집
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• 대한약학회 2005년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.231-232
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• 2005

Bacteria of Shigella spp. are responsible for shigellosis in humans, a disease characterized by destruction of the colonic epithelium that is induced by the inflammatory response elicited by invasive bacteria. They use a type III secretion system injecting effector proteins into host cells to induce their entry into epithelial cells and triggers apoptosis in macrophages. We present evidence that the effector OspG is a protein kinase that binds various ubiquitinylated ubiquitin-conjugating enzymes (E2s) and blocks degradation of phospho-$I{\kappa}B{\alpha}$ induced upon entry of bacteria into epithelial cells. Transfection experiments confirmed that OspG interferes with the $NF-{\kappa}B$ activation patway by preventing phospho-$I{\kappa}B{\alpha}$ degradation, suggesting that OspG inactivates a component of the $SCF^{{\beta}-TrCP}$ ubiquitin ligase complex (E3) involved in phospho-$I{\kappa}B{\alpha}$ ubiquitination. Upon infection of ileal loops in rabbits, the ospG mutant induced a stronger inflammatory response compared with the wild-type strain, indicating that OspG down-regulates the host innate response induced by invasive bacteria.