• 한국해양생명과학회지
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• 제2권2호
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• pp.70-74
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• 2017

IL-1RAcP는 일명 interleukin-1 receptor accessory protein이라 칭하며 interleukin-1 염증성 사이토카인과 interleukin-1 receptor I (IL-1RI) 결합체와 복합체를 형성하여 작용한다. IL-1RAcP는 면역반응, 스트레스 및 세포사멸과 관련이 있다. 본 연구의 목적은 참돔(Pagrus major)을 저수온(8℃, 33 psu) 및 저염분(20℃, 10 psu) 상태에 노출시킨 후, IL-1RAcP 유전자의 발현을 관찰하는 것이다. 연구결과, IL-1RAcP 유전자의 발현은 저수온(8℃, 33 psu) 및 저염분(20℃, 10 psu) 상태에서 유의적으로 증가하는 것으로 나타났다. 이 연구결과로서 IL-1RAcP 유전자는 저수온 및 저염분 등의 환경 스트레스에 대한 생체지표유전자로서 역할을 한다고 제의한다.

• IMMUNE NETWORK
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• 제22권6호
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• pp.49.1-49.15
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• 2022

Exosomes derived from mesenchymal stem cells (MSCs) could protect against myocardial infarction (MI). TLR4 is reported to play an important role in MI, while microRNA-182-5p (miR-182-5p) negatively regulates TLR4 expression. Therefore, we hypothesize that MSCs-derived exosomes overexpressing miR-182-5p may have beneficial effects on MI. We generated bone marrow mesenchymal stem cells (BM-MSCs) and overexpressed miR-182-5p in these cells for exosome isolation. H₂O₂-stimulated neonatal mouse ventricle myocytes (NMVMs) and MI mouse model were employed, which were subjected to exosome treatment. The expression of inflammatory factors, heart function, and TLR4 signaling pathway activation were monitored. It was found that miR-182-5p decreased TLR4 expression in BM-MSCs and NMVMs. Administration of exosomes overexpressing miR-182-5p to H₂O₂-stimulated NMVMs enhanced cell viability and suppressed the expression of inflammatory cytokines. In addition, they promoted heart function, suppressed inflammatory responses, and de-activated TLR4/NF-κB signaling pathway in MI mice. In conclusion, miR-182-5p transferred by the exosomes derived from BM-MSCs protected against MI-induced impairments by targeting TLR4.

• IMMUNE NETWORK
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• 제23권3호
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• pp.25.1-25.15
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• 2023

Mucosal environments harbour lymphocytes, which express several adhesion molecules, including intestinal homing receptors and integrin αE/β7 (CD103). CD103 binds E-cadherin, an integrin receptor expressed in intestinal endothelial cells. Its expression not only enables homing or retention of T lymphocytes at these sites but is also associated with increased T lymphocyte activation. However, it is not yet clear how CD103 expression is related to the clinical staging of breast cancer, which is determined by factors such as the size of the tumor (T), the involvement of nearby lymph nodes (N), and presence of metastasis (M). We examined the prognostic significance of CD103 by FACS in 53 breast cancer patients and 46 healthy controls enrolled, and investigated its expression, which contributes to lymphocyte recruitment in tumor tissue. Patients with breast cancer showed increased frequencies of CD103⁺, CD4⁺CD103⁺, and CD8⁺CD103⁺ cells compared to controls. CD103 was expressed at a high level on the surfaces of tumor-infiltrating lymphocytes in patients with breast cancer. Its expression in peripheral blood was not correlated with clinical TNM stage. To determine the localisation of CD103⁺ cells in breast tissue, tissue sections of breast tumors were stained for CD103. In tissue sections of breast tumors stained for CD103, its expression in T lymphocytes was higher compared to normal breast tissue. In addition, CD103⁺ cells expressed higher levels of receptors for inflammatory chemokines, compared to CD103^- cells. CD103⁺ cells in peripheral blood and tumor tissue might be an important source of tumor-infiltrating lymphocyte trafficking, homing, and retention in cancer patients.

• IMMUNE NETWORK
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• 제23권1호
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• pp.3.1-3.14
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• 2023

Microvilli are outer membrane organelles that contain cross-linked filamentous actin. Unlike well-characterized epithelial microvilli, T-cell microvilli are dynamic similar to those of filopodia, which grow and shrink intermittently via the alternate actin-assembly and -disassembly. T-cell microvilli are specialized for sensing Ags on the surface of Ag-presenting cells (APCs). Thus, these finger-shaped microprotrusions contain many signaling-related proteins and can serve as a signaling platforms that induce intracellular signals. However, they are not limited to sensing external information but can provide sites for parts of the cell-body to tear away from the cell. Cells are known to produce many types of extracellular vesicles (EVs), such as exosomes, microvesicles, and membrane particles. T cells also produce EVs, but little is known about under what conditions T cells generate EVs and which types of EVs are released. We discovered that T cells produce few exosomes but release large amounsts of microvilli-derived particles during physical interaction with APCs. Although much is unanswered as to why T cells use the same organelles to sense Ags or to produce EVs, these events can significantly affect T cell fate, including clonal expansion and death. Since TCRs are localized at microvilli tips, this membrane event also raises a new question regarding long-standing paradigm in T cell biology; i.e., surface TCR downmodulation following T cell activation. Since T-cell microvilli particles carry T-cell message to their cognate partner, these particles are termed T-cell immunological synaptosomes (TISs). We discuss the potential physiological role of TISs and their application to immunotherapies.

• IMMUNE NETWORK
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• 제22권6호
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• pp.51.1-51.20
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• 2022

Trypanosoma cruzi, the etiological agent of Chagas disease, is an intracellular protozoan parasite, which is now present in most industrialized countries. About 40% of T. cruzi infected individuals will develop severe, incurable cardiovascular, gastrointestinal, or neurological disorders. The molecular mechanisms by which T. cruzi induces cardiopathogenesis remain to be determined. Previous studies showed that increased IL-6 expression in T. cruzi patients was associated with disease severity. IL-6 signaling was suggested to induce pro-inflammatory and pro-fibrotic responses, however, the role of this pathway during early infection remains to be elucidated. We reported that T. cruzi can dysregulate the expression of host PIWI-interacting RNAs (piRNAs) during early infection. Here, we aim to evaluate the dysregulation of IL-6 signaling and the piRNAs computationally predicted to target IL-6 molecules during early T. cruzi infection of primary human cardiac fibroblasts (PHCF). Using in silico analysis, we predict that piR_004506, piR_001356, and piR_017716 target IL6 and SOCS3 genes, respectively. We validated the piRNAs and target gene expression in T. cruzi challenged PHCF. Secreted IL-6, soluble gp-130, and sIL-6R in condition media were measured using a cytokine array and western blot analysis was used to measure pathway activation. We created a network of piRNAs, target genes, and genes within one degree of biological interaction. Our analysis revealed an inverse relationship between piRNA expression and the target transcripts during early infection, denoting the IL-6 pathway targeting piRNAs can be developed as potential therapeutics to mitigate T. cruzi cardiomyopathies.

• The Korean Journal of Pain
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• 제37권2호
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• pp.91-106
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• 2024

The mechanisms of the chronic pain and depression comorbidity have gained significant attention in recent years. The complement system, widely involved in central nervous system diseases and mediating non-specific immune mechanisms in the body, remains incompletely understood in its involvement in the comorbidity mechanisms of chronic pain and depression. This review aims to consolidate the findings from recent studies on the complement system in chronic pain and depression, proposing that it may serve as a promising shared therapeutic target for both conditions. Complement proteins C1q, C3, C5, as well as their cleavage products C3a and C5a, along with the associated receptors C3aR, CR3, and C5aR, are believed to have significant implications in the comorbid mechanism. The primary potential mechanisms encompass the involvement of the complement cascade C1q/C3-CR3 in the activation of microglia and synaptic pruning in the amygdala and hippocampus, the role of complement cascade C3/C3a-C3aR in the interaction between astrocytes and microglia, leading to synaptic pruning, and the C3a-C3aR axis and C5a-C5aR axis to trigger inflammation within the central nervous system. We focus on studies on the role of the complement system in the comorbid mechanisms of chronic pain and depression.

• IMMUNE NETWORK
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• 제21권5호
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• pp.37.1-37.17
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• 2021

Hepatitis B virus X (HBx) protein has been reported as a key protein regulating the pathogenesis of HBV-induced hepatocellular carcinoma (HCC). Recent evidence has shown that HBx is implicated in the activation of autophagy in hepatic cells. Nevertheless, the precise molecular and cellular mechanism by which HBx induces autophagy is still controversial. Herein, we investigated the molecular and cellular mechanism by which HBx is involved in the TRAF6-BECN1-Bcl-2 signaling for the regulation of autophagy in response to TLR4 stimulation, therefore influencing the HCC progression. HBx interacts with BECN1 (Beclin 1) and inhibits the association of the BECN1-Bcl-2 complex, which is known to prevent the assembly of the pre-autophagosomal structure. Furthermore, HBx enhances the interaction between VPS34 and TRAF6-BECN1 complex, increases the ubiquitination of BECN1, and subsequently enhances autophagy induction in response to LPS stimulation. To verify the functional role of HBx in liver cancer progression, we utilized different HCC cell lines, HepG2, SK-Hep-1, and SNU-761. HBx-expressing HepG2 cells exhibited enhanced cell migration, invasion, and cell mobility in response to LPS stimulation compared to those of control HepG2 cells. These results were consistently observed in HBx-expressed SK-Hep-1 and HBx-expressed SNU-761 cells. Taken together, our findings suggest that HBx positively regulates the induction of autophagy through the inhibition of the BECN1-Bcl-2 complex and enhancement of the TRAF6-BECN1-VPS34 complex, leading to enhance liver cancer migration and invasion.

• IMMUNE NETWORK
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• 제21권6호
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• pp.44.1-44.15
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• 2021

Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide half-life in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2K^b molecules, and then the natural peptide epitopes associated with the H-2K^b molecules were exchanged with a model tumor peptide, SIINFEKL (OVA_257-268). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H2K^b complex-specific CD8⁺ T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKL-specific CD8⁺ T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.

• IMMUNE NETWORK
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• 제22권2호
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• pp.15.1-15.16
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• 2022

Foreign molecules, including viruses and bacteria-derived toxins, can also induce airway inflammation. However, to the best of our knowledge, the roles of these molecules in the development of airway inflammation have not been fully elucidated. Herein, we investigated the precise role and synergistic effect of virus-mimicking double-stranded RNA (dsRNA) and staphylococcal enterotoxin B (SEB) in macrophages and epithelial cells. To identify cytokine expression profiles, both the THP-1-derived macrophages and BEAS-2B epithelial cells were stimulated with dsRNA or SEB. A total of 21 cytokines were evaluated in the culture supernatants. We observed that stimulation with dsRNA induced cytokine production in both cell types. However, cytokine production was not induced in SEB-stimulated epithelial cells, compared to the macrophages. The synergistic effect of dsRNA and SEB was evaluated observing cytokine level and intracellular phospho-signaling. Fifteen different types were detected in high-dose dsRNA-stimulated epithelial cells, and 12 distinct types were detected in macrophages; those found in macrophages lacked interferon production compared to the epithelial cells. Notably, a synergistic effect of cytokine induction by co-stimulation of dsRNA and SEB was observed mainly in epithelial cells, via activation of most intracellular phosphor-signaling. However, macrophages only showed an accumulative effect. This study showed that the type and severity of cytokine productions from the epithelium or macrophages could be affected by different intensities and a combination of dsRNA and SEB. Further studies with this approach may improve our understanding of the development and exacerbation of airway inflammation and asthma.

• IMMUNE NETWORK
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• 제22권3호
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• pp.25.1-25.11
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• 2022

IL-34 can promote osteoclast differentiation and activation, which may contribute to steroid-induced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.