• 생명과학회지
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• 제30권9호
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• pp.826-833
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• 2020

Phospholipase C gamma (PLCγ)는 phosphatidylinositol을 가수분해하여 신호전달 과정에 참여하는 PLC의 주요한 isotype으로 γ-specific array의 특징적인 구조를 바탕으로 receptor tyrosine kinases 및 non-receptor tyrosine kinase 신호를 주로 매개한다. PLCγ1과 PLCγ2의 두 isozyme이 존재하며 다양한 세포에서 발현하여 cell proliferation, migration 및 differentiation 등 여러 세포작용을 조절하고 있다. 최근의 연구들에서 PLCγ 돌연변이가 cancer와 immune disease 및 brain disorder 등에 연관된다는 것이 밝혀지고 있으며 genetic model을 통해 PLCγ의 생리적·병리적 기능이 제시되었다. 본 리뷰에서는 최신의 연구 결과들을 바탕으로 PLCγ의 구조와 활성 조절 기전에 대해 기술하고 나아가 여러 질병의 발병과 진행에서 보고된 PLCγ의 돌연변이와 knockout 마우스를 활용한 연구 결과를 바탕으로 생리적·병리적 관점에서 PLCγ의 역할에 대해 고찰하였다.

• Tuberculosis and Respiratory Diseases
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• 제40권2호
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• pp.197-202
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• 1993

저자들은 37세의 여자에서 스테로이드치료에 저항을 보이다가 prednisolone과 cyclophosphamide 병합투여로 치료반응을 보인 간질성폐질환을 동반한 다발성근염 1예를 경험하였기에 이를 문헌 고찰과 함께 보고하는 바이다.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2008년도 International Meeting of the Microbiological Society of Korea
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• pp.62-64
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• 2008

A major hurdle to the development of RNA interference as therapy for HIV infection is the delivery of siRNA to T lymphocytes which are difficult cells to transfect even in vitro. We have employed a single chain antibody to the pan T cell surface antigen CD7 was conjugated to an oligo-9-arginine peptide (scFvCD7-9R) for T cell-specific siRNA delivery in NOD/SCIDIL2${\gamma}$-/- mice reconstituted with human peripheral blood lymphocytes (Hu-PBL). Using a novel delivery, we first show that scFvCD7-9R efficiently delivered CD4 siRNA into human T cells in vitro. In vivo administration to Hu-PBL mice resulted in reduced levels of surface CD4 expression on T cells. Mice infected with HIV-1 and treated on a weekly basis with scFvCD7-9R-siRNA complexes targeting a combination of viral genes and the host coreceptor molecule CCR5 successfully maintained CD4/CD3 T cell ratios up to 4 weeks after infection in contrast to control mice that displayed a marked reduction in CD4 T cell numbers. p24 antigen levels were undetectable in 3 of the 4 protected mice. scFvCD7-9R/antiviral siRNA treatment also helped maintain CD4 T cell numbers with reduced plasma viral loads in Hu-PBL mice reconstituted with PBMC from donors seropositive for HIV, indicating that this method can contain viral replication even in established HIV infections. Our results show that scFvCD7-9R could be further developed as a potential therapeutic for HIV-1 infection.

• Journal of Periodontal and Implant Science
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• 제52권1호
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• pp.28-38
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• 2022

Purpose: Macrophages play crucial roles as early responders to bacterial pathogens and promote/ or impede chronic inflammation in various tissues. Periodontal macrophage-induced pyroptosis results in physiological and pathological inflammatory responses. The transcription factor Dec2 is involved in regulating immune function and inflammatory processes. To characterize the potential unknown role of Dec2 in the innate immune system, we sought to elucidate the mechanism that may alleviate macrophage pyroptosis in periodontal inflammation. Methods: Porphyromonas gingivalis lipopolysaccharide (LPS) was used to induce pyroptosis in RAW 264.7 macrophages. Subsequently, we established an LPS-stimulated Dec2 overexpression cellular model in macrophages. Human chronic periodontitis tissues were employed to evaluate potential changes in inflammatory marker expression and pyroptosis. Finally, the effects of Dec2 deficiency on inflammation and pyroptosis were characterized in a P. gingivalis-treated experimental periodontitis Dec2-knockout mouse model. Results: Macrophages treated with LPS revealed significantly increased messenger RNA expression levels of Dec2 and interleukin (IL)-1β. Dec2 overexpression reduced IL-1β expression in macrophages treated with LPS. Overexpression of Dec2 also repressed the cleavage of gasdermin D (GSDMD), and the expression of caspase-11 was concurrently reduced in macrophages treated with LPS. Human chronic periodontitis tissues showed significantly higher gingival inflammation and pyroptosis-related protein expression than non-periodontitis tissues. In vivo, P. gingivalis-challenged mice exhibited a significant augmentation of F4/80, tumor necrosis factor-α, and IL-1β. Dec2 deficiency markedly induced GSDMD expression in the periodontal ligament of P. gingivalis-challenged mice. Conclusions: Our findings indicate that Dec2 deficiency exacerbated P. gingivalis LPS-induced periodontal inflammation and GSDMD-mediated pyroptosis. Collectively, our results present novel insights into the molecular functions of macrophage pyroptosis and document an unforeseen role of Dec2 in pyroptosis.

• 대한수의학회지
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• 제31권2호
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• pp.155-161
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• 1991

The mechanisms of demyelination in Theiler's murine encephalomyelitis virus (TMEV)-induced chronic central nervous system(CNS) disease are still unclear and are probably multifactoral. This study was intended to culture spinal cord cells isolated from TMEV-induced demyelinating mice. By Percoll density centrifugation of enzymatically dissociated tissue, the cells were collected and then cultured on poly-L-lysine-coated plastic coverslips for 2 weeks. Oligodendrocytes, astrocytes and macrophages were identified using cell-type specific markers. Viral antigens were not present in oligodendrocytes and in astrocytes by double immunofluorescence. Affected mouse oligodendrocytes had less capacities of sheet formation and galactocerebroside immunoreactivity than those of control cell 3. These findings support the hypothesis that immune mediated mechanisms play an important role in the process of demyelination in this animal model.

• Annals of Clinical Neurophysiology
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• 제4권2호
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• pp.98-107
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• 2002

Multifocal motor neuropathy (MMN) is a chronic immune-mediated peripheral myelinopathy. The major clinical features include slowly progressive, painless, and asymmetric weakness, usually of distal limb muscle. Early in the course of the disease, weakness is not necessarily associated with muscle atrophy, owing to the initial primary involvement of peripheral myelin. Chronic progressive weakness is often associated with some degree of concurrent axonal loss and subsequent muscle atrophy. Sensory symptoms are usually mild or absent, and involvement of cranial and respiratory muscles is rare. The findings of multifocal motor conduction block, abnormal temporal dispersion, and focal conduction slowing at segments not at risk for common entrapment or compression injury, associated with normal sensory conduction studies along the same segments, are the hallmark electrophysiologic features of MMN. The slow progression and absence of upper motor neuron signs are the major clinical points that separate MMN from amyotrophic lateral sclerosis. The role of GM1 antibodies, found in high titers in 22~84% of MMN patients, remains uncertain. The contention that MMN is an autoimmune disorder is largely based on the often dramatic improvement in symptoms following the administration of intravenuos immunoglobulin or cyclophosphamide.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.7-13
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• 2001

Arthritis may be broadly classified as degenerative - related to defects in cartilage and other joint constituents, often age-associated - or inflammatory disease. Inflammatory arthritis called as rheumatoid arthritis (RA) is a chronic inflammatory arthropathy and characterized by a destructive arthritis. RA encompasses infectious arthritis, arthritis caused by intra-articular deposits of crystalline material (gout), syndromes associated with genetic defects (familial Mediterranean fever), and the immune-mediated inflammatory arthropathy. Degenerative arthritis called as osteoarthritis (OA), which is most frequently occurring, causes degenerative figures of knee, waist and knuckle, and accompanies severe pain around the cartilage. Also, it may cause morning stiffness, gelling effect, tenderness, bone swelling, crepitus, and motion disorders.

• Childhood Kidney Diseases
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• 제23권1호
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• pp.1-6
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• 2019

Nephrotic syndrome (NS) is the most common glomerular disorder in childhood, and a vast majority of cases are idiopathic. The precise cause of this common childhood disease is not fully elucidated despite significant advancements in our understanding of podocyte biology. Idiopathic NS has been considered "a disorder of T-cell function" mediated by a circulating factor that alters podocyte function resulting in massive proteinuria since the last four decades. Several circulatory factors released from T-cells are considered to be involved in pathophysiology of NS; however, a single presumptive factor has not been defined yet. Extended evidence obtained by advances in the pathobiology of podocytes has implicated podocytes as critical regulator of glomerular protein filtration and podocytopathy. The candidate molecules as pathological mediators of steroid-dependent NS are CD80 (also known as B7-1), hemopexin, and angiopoietin-like 4. The "two-hit" hypothesis proposes that the expression of CD80 on podocytes and ineffective inhibition of podocyte CD80 due to regulatory T-cell dysfunction or impaired autoregulation by podocytes results in NS. Recent studies suggest that not only T cells but also other immune cells and podocytes are involved in the pathogenesis of MCNS.

• Journal of Ginseng Research
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• 제46권6호
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• pp.722-730
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• 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogenic virus that causes coronavirus disease 2019 (COVID-19), with major symptoms including hyper-inflammation and cytokine storm, which consequently impairs the respiratory system and multiple organs, or even cause death. SARS-CoV-2 activates inflammasomes and inflammasome-mediated inflammatory signaling pathways, which are key determinants of hyperinflammation and cytokine storm in COVID-19 patients. Additionally, SARS-CoV-2 inhibits inflammasome activation to evade the host's antiviral immunity. Therefore, regulating inflammasome initiation has received increasing attention as a preventive measure in COVID-19 patients. Ginseng and its major active constituents, ginsenosides and saponins, improve the immune system and exert anti-inflammatory effects by targeting inflammasome stimulation. Therefore, this review discussed the potential preventive and therapeutic roles of ginseng in COVID-19 based on its regulatory role in inflammasome initiation and the host's antiviral immunity.

• Annals of Clinical Neurophysiology
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• 제24권2호
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• pp.59-62
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• 2022

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic recurrent acquired immune-mediated disease of the peripheral nerves that presents with progressive sensory and motor deficits in all four limbs. Cranial nerve involvement is not as common as in Guillain-Barre syndrome, and central nervous system involvement including optic neuritis has rarely been reported in patients with CIDP. We recently experienced a case with classic CIDP involving bilateral facial and trigeminal nerves, right lower cranial nerves, and the right optic nerve.