• 제목/요약/키워드: Immunological diseases

검색결과 188건 처리시간 0.028초

Extracellular Acidification Augments NLRP3-Mediated Inflammasome Signaling in Macrophages

  • Byeong Jun Chae;Kyung-Seo Lee;Inhwa Hwang;Je-Wook Yu
    • IMMUNE NETWORK
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    • 제23권3호
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    • pp.23.1-23.17
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    • 2023
  • Inflammation is a series of host defense processes in response to microbial infection and tissue injury. Inflammatory processes frequently cause extracellular acidification in the inflamed region through increased glycolysis and lactate secretion. Therefore, the immune cells infiltrating the inflamed region encounter an acidic microenvironment. Extracellular acidosis can modulate the innate immune response of macrophages; however, its role for inflammasome signaling still remains elusive. In the present study, we demonstrated that macrophages exposed to an acidic microenvironment exhibited enhanced caspase-1 processing and IL-1β secretion compared with those under physiological pH. Moreover, exposure to an acidic pH increased the ability of macrophages to assemble the NLR family pyrin domain containing 3 (NLRP3) inflammasome in response to an NLRP3 agonist. This acidosis-mediated augmentation of NLRP3 inflammasome activation occurred in bone marrow-derived macrophages but not in bone marrow-derived neutrophils. Notably, exposure to an acidic environment caused a reduction in the intracellular pH of macrophages but not neutrophils. Concordantly, macrophages, but not neutrophils, exhibited NLRP3 agonist-mediated translocation of chloride intracellular channel protein 1 (CLIC1) into their plasma membranes under an acidic microenvironment. Collectively, our results demonstrate that extracellular acidosis during inflammation can increase the sensitivity of NLRP3 inflammasome formation and activation in a CLIC1-dependent manner. Thus, CLIC1 may be a potential therapeutic target for NLRP3 inflammasome-mediated pathological conditions.

아토피와 알러지에 대한 한의학적 약물치료의 혈액면역학적 개선효과 (Effects of Herbal Prescriptions on the Immunological Parameter in Patients with Atopic & Allergic Diseases; Clinical Observational Study)

  • 조현익;신병철;김형일
    • 동의생리병리학회지
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    • 제21권6호
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    • pp.1646-1654
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    • 2007
  • The aim of this study was to investigate the effects of several herbal prescriptions in patients with allergy or atopic disease, such as atopic dermatitis, asthma and allergy rhinitis and others, on the blood immunological parameters and to verify the safety of long-term use of herbal medicine. Eighty one patients with allergy or atopy disease who taken herbal medicine at least for 2 months were compared with patients who taken same medicine with no allergy & atopy disease (n=14) and normal healthy subjects (n=22). According to the comparison of immunological parameters change, the data showed that herbal medicine decreased IgE (P=0.003), Eosinophil ratio (P<0.001) and count (P<0.001) of White Blood Cell (WBC) and did not affect to the liver cell enzymes in blood. This results indicated that herbal medicine decreased immune hypersensitivity and improved chronic inflammation related to blood immunological parameters of allergy or atopy diseases. In addition, herbal medicine seemed to be safe to the liver function for long-term use.

류마티스양 관절염 환자 활막 T 세포의 T 세포수용체 β쇄 분석 (Usage of T Cell Receptor Repertoire is Restricted in Synovial Lymphocytes in Rheumatoid Arthritis)

  • 권대호;이수곤;김세종;최인홍
    • IMMUNE NETWORK
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    • 제1권1호
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    • pp.70-76
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    • 2001
  • Background: Rheumatoid arthritis is an autoimmune disease characterized by a chronic inflammatory process, primarily involving the synovial membrane of peripheral j oints, where T cell activation is found. To address the superantigen stimulation in rheumatoid arthritis, T cell clonality and the expression of activation markers were analyzed. Methods: To detect TCRB V usage, inverse PCR and sequencing were done. Monoclonal antibodies were used for flow cytometric analysis of TCRBV8 or TCRBV5. As results, a restricted usage of TCRBV3 gene was detected in synovial lymphocytes from one rheumatoid arthritis patient. However, preferential usage for TCRB V8, which may be one indicator for stimulation by staphylococcal superantigen, was not obvious although general activation of T cells was found as high DR+ percentage in synovial T cells. These data show specific antigen rather than superantigen might involve the pathogenesis of rheumatoid arthritis.

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IFN-γ Regulates Expression of BRG1 Associated Factor 155/170 and Sensitivity to Steroid in Astrocytes

  • Lim, Jung-Hee;Lee, Jeonggi;Park, Joo Young;Choi, In-Hong
    • IMMUNE NETWORK
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    • 제4권4호
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    • pp.224-228
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    • 2004
  • Background: The expression of BRG1 associated factors (BAF) 155 and BAF 170 in response to $IFN-{\gamma}$ or $TNF-{\alpha}$ was studied in astrocytoma cell lines and primary astrocytes. BAFs are complexed with BRG1 and are also associated with activated glucocorticoid for glucocorticoid trans-activation. Methods: $IFN-{\gamma}$ was pretreated for 18 hrs and cells were incubated with IL-1 or $TNF-{\alpha}$ for 72 hrs or 96 hrs with different concentrations of steroid. Cell death was measured by LDH assay. BAF expression was assayed by RT-PCR. Results: $IFN-{\gamma}$ increased cell death by dexamethasone in LN215 cells but not in LN319 cells. The $IFN-{\gamma}$ increased the expression of BAF 155 and BAF 170 in adult astrocytes and LN215 cells, but $IFN-{\gamma}$ decreased the expression of BAF 155/170 in LN319 cells. The effect of $IFN-{\gamma}$ on the expression of BAF was not as clear in fetal astrocytes as it was in adult astrocytes. Conclusion: Our results suggest cytokines produced during immune reaction or immunotherapy may modulate steroid susceptibility of astrocytes and astrocytoma cells by influencing the expression of BAFs.

An inhibitory alternative splice isoform of Toll-like receptor 3 is induced by type I interferons in human astrocyte cell lines

  • Seo, Jin-Won;Yang, Eun-Jeong;Kim, Se Hoon;Choi, In-Hong
    • BMB Reports
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    • 제48권12호
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    • pp.696-701
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    • 2015
  • Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA. It stimulates pro-inflammatory cytokine and interferon production. Here we reported the expression of a novel isoform of TLR3 in human astrocyte cell lines whose message is generated by alternative splicing. The isoform represents the N-terminus of the protein. It lacks many of the leucine-rich repeat domains, the transmembrane domain, and the intracellular Toll/interleukin-1 receptor domain of TLR3. Type I interferons (interferon-α and interferon-β) induced the expression of this isoform. Exogenous overexpression of this isoform inhibited interferon regulatory factor 3, signal transducers and activators of transcription 1, and Inhibitor of kappa B α signaling following stimulation. This isoform of TLR3 also inhibited the production of chemokine interferon-γ-inducible protein 10. Our study clearly demonstrated that the expression of this isoform of TLR3 was a negative regulator of signaling pathways and that it was inducible by type I interferons. We also found that this isoform could modulate inflammation in the brain.

규칙적인 수영훈련이 마우스 비장세포의 ROS생성과 림프구 증식에 미치는 영향 (The Effects of Swimming Training on Lymphocyte Proliferation and ROS Production in Spleen Lymphocytes of BALB/c Mice)

  • 곽이섭;박전한;김세종;장윤수;이봉기
    • IMMUNE NETWORK
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    • 제2권2호
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    • pp.96-101
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    • 2002
  • Background: Aerobic training can be defined as any physical exercise that increases the heart rate and enhances the body's intake of oxygen long enough to benefit the condition of body. Running, cycling, and swimming are examples of aerobic activities. This type of exercise optimises immune functions. Recently several experimental findings suggested that the regular swimming training increase immune response, but there have been very few reports which compare warm water exercise with cold water exercise in spleen lymphocytes. Methods: This study was designed to examine the effects of regular swimming training on Index, the number of lymphocytes, proliferative activity and production of reactive oxygen species (ROS) by splenocytes in BALB/c mice. Thirty six mice (6 week old) were performed 10 weeks of regular swimming training and they were divided into 6 groups according to the regular swimming training (CRG: control resting group, CEG: control exercise group, WRG: warm water trained resting group, WEG: warm water trained exercise group, CORG: cold water trained resting group, COEG: cold water exercise group). Analytical items were weight change, spleen index, the number of lymphocytes, proliferative activity and production of ROS. All data were expressed as mean and standard deviation by using SPSS package program (ver. 10.0). Results: The swimming training significantly decreased body weight, and increased spleen index, the number of lymphocytes and proliferative activity in the presence or absence of Con A and LPS added conditions. For the WRG and CORG, the quantity of ROS from splenocytes was higher than CRG, whereas, ROS by spleen lymphocytes was lower following 90 min acute exercise stress. Conclusion: These results suggested that the swimming training not only increases the number of lymphocytes but also increases proliferative activity by splenocytes in vitro.

Ribosomal Protein L19 and L22 Modulate TLR3 Signaling

  • Yang, Eun-Jeong;Seo, Jin-Won;Choi, In-Hong
    • IMMUNE NETWORK
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    • 제11권3호
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    • pp.155-162
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    • 2011
  • Background: Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA) and induces inflammation. In this study we attempted to ascertain if there are endogenous host molecules controlling the production of cytokines and chemokines. Two candidates, ribosomal protein L19 and L22, were analyzed to determine if they influence cytokine production followed by TLR3 activation. In this study we report that L19 acts upon production of IP-10 or IL-8 differently in glioblastoma cells. Methods: L19 or L22 was transfected into HEK293-TLR3, A549 or A172 cells. After treatment with several inhibitors of NF-${\kappa}B$, PI3K, p38 or ERK, production of IL-8 or IP-10 was measured by ELISA. siRNA was introduced to suppress expression of L19. After Vesicular stomatitis virus infection, viral multiplication was measured by western blot. Results: L19 increased ERK activation to produce IL-8. In A172 cells, in which TLR3 is expressed at endosomes, L19 inhibited interferon regulatory factor 3 (IRF3) activation and IP-10 production to facilitate viral multiplication, whereas L19 inhibited viral multiplication in A549 cells bearing TLR3 on their cell membrane. Conclusion: Our results suggest that L19 regulates TLR3 signaling, which is cell type specific and may be involved in pathogenesis of autoimmune diseases and chronic inflammatory diseases.

Regulation of Immunological Effect of Rubia cordifolia Extract and Associated MAPKs Pathway in RBL-2H3 Cell-line

  • Jeong, Eunbee;Lee, Deug-Chan
    • 한국자원식물학회지
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    • 제30권6호
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    • pp.662-669
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    • 2017
  • Rubia cordifolia has been used to treat diseases for many years in China and India. Although the biological properties and major compounds of R. cordifolia have been extensively studied, the underlying mechanisms of its biological effects remain elusive. In terms of immunological effects, anti-inflammation effect of macrophage (Raw 264.7) simply has been reported. In this study, R. cordifolia was extracted in 70% ethanol and the extract did not affect to macrophage (Raw 264.7) pro-inflammation and T cell (Molt-4). However, in mast cell (RBL-2H3), it showed inhibition of degranulation. The inducing inhibitory effect on degranulation was related to concentration dependent variation in phosphorylation of ERK-1/2 and upregulating the JNK phosphorylation in RBL-2H3 cells. Based on these data, we concluded that R. cordifolia newly have anti-allergenic effects in RBL-2H3 and might be used as a therapeutic agent to treat or prevent allergic diseases such as asthma and atopic dermatitis.

Increased B Cell Understanding Puts Improved Vaccine Platforms Just Over the Horizon

  • Geneva Rose Notario;Kihyuck Kwak
    • IMMUNE NETWORK
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    • 제22권6호
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    • pp.47.1-47.20
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    • 2022
  • In the face of an endlessly expanding repertoire of Ags, vaccines are constantly being tested, each more effective than the last. As viruses and other pathogens evolve to become more infectious, the need for efficient and effective vaccines grows daily, which is especially obvious in an era that is still attempting to remove itself from the clutches of the severe acute respiratory syndrome coronavirus 2, the cause of coronavirus pandemic. To continue evolving alongside these pathogens, it is proving increasingly essential to consider one of the main effector cells of the immune system. As one of the chief orchestrators of the humoral immune response, the B cell and other lymphocytes are essential to not only achieving immunity, but also maintaining it, which is the vital objective of every vaccine.