• Title/Summary/Keyword: immune-mediated disease

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Tilianin Inhibits MUC5AC Expression Mediated Via Down-Regulation of EGFR-MEK-ERK-Sp1 Signaling Pathway in NCI-H292 Human Airway Cells

  • Song, Won-Yong;Song, Yong-Seok;Ryu, Hyung Won;Oh, Sei-Ryang;Hong, JinTae;Yoon, Do-Young
    • Journal of Microbiology and Biotechnology
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    • v.27 no.1
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    • pp.49-56
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    • 2017
  • In the human airway, mucus exists to protect the respiratory system as a primary barrier of the innate immune system. However, hyperexpressed mucus limits airflow, resulting in a decrease of lung function. Among more than 20 mucin family members, MUC5AC and MUC5B are major glycoproteins in human airway mucus. The epidermal growth factor receptor (EGFR) signaling pathway is one of the mechanisms of these mucins expression and specificity protein-1 (Sp1) transcription factor is the downstream signal of this pathway, playing pivotal roles in mucin expression. Even though there are some drugs for treating mucus hypersecretion, no drug has proven effects on humans. We found that the flavonoid tilianin regulated MUC5AC expression and also inhibited Sp1 phosphorylation. In this study, we investigated how tilianin would modulate EGFR signaling and regulate mucin production. In conclusion, tilianin inhibited MUC5AC expression mediated via modulating the EGFR-MEK-ERK-Sp1 signaling pathway in NCI-H292 human airway epithelial cells. This study may provide the basis for the novel treatment of mucus hypersecretion.

The Role of Yoga Intervention in the Treatment of Allergic Rhinitis: A Narrative Review and Proposed Model

  • Chauhan, Ripudaman Singh;Rajesh, S.K
    • CELLMED
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    • v.10 no.3
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    • pp.25.1-25.7
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    • 2020
  • Allergic Rhinitis (AR) is an IgE (immunoglobin-E) mediated inflammatory condition of upper respiratory tract; main clinical features involve runny nose, sneezing, nasal obstruction, itching and watery eyes. AR is a global problem and has large variations in incidences, currently affects up to 20% - 40% of the population worldwide. It may not be a life-threatening disease per se but indisposition from the condition can be severe and has the potential to adversely affect the daily functioning of life. Classical yoga literature indicates that, components of yoga have been used to treat numerous inflammatory conditions including upper respiratory tract. A few yoga intervention studies reported improvement in lung capacity, Nasal air flow and symptoms of allergic rhinitis. This review examined various anti-inflammatory pathways mediated through Yoga that include downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines. The hypothalaminic-pitutary-adrenal (HPA) axis and vagal efferent stimulation has been reported to mediate anti-inflammatory effect. A significant reduction is also reported in other inflammatory biomarkers like- TNF-alpha, nuclear factor kappa B (NF-κB), plasma CRP and Cortisol level. Neti, a yogic nasal cleansing technique, reported beneficial effect on AR by direct physical cleansing of thick mucus, allergens, and inflammatory mediator from nasal mucosa resulting in improved ciliary beat frequency. We do not find any study showing effect of yoga on neurogenic inflammation. In summary, Integrated Yoga Therapy may have beneficial effect in reducing symptoms and improving quality of life for patients with allergic rhinitis. Yoga may reduce inflammation through mediating neuro-endocrino-immunological network. Future studies are needed to explore the mechanism how yoga might modulate immune inflammation cascade and neurogenic inflammation at the cellular level in relevance to allergic rhinitis; the effects of kriyas (yogic cleansing techniques) also need to be evaluated in early and late phase of AR. So the proposed model could guide future research.

IL-8/CXCL8 Upregulates 12-Lipoxygenase Expression in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats

  • Kim, Jung-Hae;Kang, Young-Jin;Kim, Hee-Sun
    • IMMUNE NETWORK
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    • v.9 no.3
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    • pp.106-113
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    • 2009
  • Background: We previously demonstrated remarkable differences in the expression of IL-8/CXCL8 in aortic tissues and vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) compared to VSMC from normotensive Wistar-Kyoto rats (WKY). In the present study, we investigated the direct effect of IL-8/CXCL8 on expression of 12-lipoxygenase (LO), a hypertensive modulator, in SHR VSMC. Methods: Cultured aortic VSMC from SHR and WKY were used. Expression of 12-LO mRNA was determined by real-time polymerase chain reaction. Phosphorlyation of ERK1/2 and production of 12-LO and angiotensin II subtype 1 ($AT_1$) receptor were assessed by Western blots. IL-8/CXCL8-stimulated DNA synthesis was determined by measuring incorporation of [$^3H$]-thymidine. And effect of IL-8/CXCL8 on vascular tone was determined by phenylephrine-induced contraction of thoracic aortic rings. Results: Treatment with IL-8/CXCL8 greatly increased 12-LO mRNA expression and protein production compared to treatment with angiotensin II. IL-8/CXCL8 also increased the expression of the $AT_1$ receptor. The increase in 12-LO induced by IL-8/CXCL8 was inhibited by treatment with an $AT_1$ receptor antagonist. The induction of 12-LO mRNA production and the proliferation of SHR VSMC by IL-8/CXCL8 was mediated by the ERK pathway. The proliferation of SHR VSMC and the vascular contraction in the thoracic aortic ring, both of which were induced by IL-8/CXCL8, were inhibited by baicalein, a 12-LO inhibitor. Conclusion: These results suggest that the potential role of IL-8/CXCL8 in hypertensive processes is likely mediated through the 12-LO pathway.

Leptin potentiates Prevotella intermedia lipopolysaccharide-induced production of TNF-$\alpha$ in monocyte-derived macrophages

  • Kim, Sung-Jo
    • Journal of Periodontal and Implant Science
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    • v.40 no.3
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    • pp.119-124
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    • 2010
  • Purpose: In addition to regulating body weight, leptin is also recognized for its role in the regulation of immune function and inflammation. The purpose of this study was to investigate the effect of leptin on Prevotella (P.) intermedia lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-$\alpha$ production in differentiated THP-1 cells, a human monocytic cell line. Methods: LPS from P. intermedia ATCC 25611 was prepared by the standard hot phenol-water method. THP-1 cells were incubated in the medium supplemented with phorbol myristate acetate to induce differentiation into macrophage-like cells. The amount of TNF-$\alpha$ and interleukin-8 secreted into the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). TNF-$\alpha$ and Ob-R mRNA expression levels were determined by semi-quantitative reverse transcription-polymerase chain reaction analysis. Results: Leptin enhanced P. intermedia LPS-induced TNF-$\alpha$ production in a dose-dependent manner. Leptin modulated P. intermedia LPS-induced TNF-$\alpha$ expression predominantly at the transcriptional level. Effect of leptin on P. intermedia LPS-induced TNF-$\alpha$ production was not mediated by the leptin receptor. Conclusions: The ability of leptin to enhance P. intermedia LPS-induced TNF-$\alpha$ production may be important in the establishment of chronic lesion accompanied by osseous tissue destruction observed in inflammatory periodontal disease.

Acute Disseminated Encephalomyelitis(ADEM) Presenting as Multiple Cystic Lesions - A Case Report - (다발성 낭종성 병변을 보인 급성 파종성 뇌척수염 - 증례보고 -)

  • Kim, Dae Won;Kim, Tae Young;Kim, Jong Moon;Yun, Ki Jung
    • Journal of Korean Neurosurgical Society
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    • v.30 no.5
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    • pp.622-626
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    • 2001
  • Acute disseminated encephalomyelitis(ADEM) is an uncommon immune-mediated inflammatory demyelinating disorder that typically affects the white matter of the central nervous system. Radiologic findings of acute disseminated encephalomyelitis are not pathognomomic. The differential diagnosis is always difficult. Occasionally, the clinical features, radiological and histopathological findings of patients with acute disseminated encephalomyelitis mimic the brain tumor or other space occupying lesions. The authors report a 6-year-old girl who presented with right hemiparesis two days after nausea and vomiting. Brain MRI of the patient revealed non-enhanced multiple cystic lesions in subcortical white matter of both cerebral hemisphere with prominent edema. One of the cystic lesions was resected to differentiate with metastatic tumor or inflammatory disease such as abscess and confirmed as the acute disseminated encephalomyelitis via various immunohistochemical stains. Pertinent literature is reviewed with discussion on this uncommon ADEM associated with multiple cystic lesions.

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Immunological Changes on Allergic Response after Beevenom Immunotherapy (봉독 면역요법후의 면역학적 변화에 대한 고찰 -알레르기 질환에 응용 가능성을 중심으로-)

  • Han, Dong-Ha
    • Journal of Pharmacopuncture
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    • v.7 no.3
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    • pp.27-35
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    • 2004
  • Beevenom immunotherapy(BVIT) in allergic patients is a well-established treatment modality for the prevention of systemic anaphylactic reactions caused by insect stings. BVIT is accompanied by increases in allergen-specific IgG, particularly the IgG4 isotype, which blocks not only IgE-dependent histamine release from basophils but also IgE-mediated antigen presentation to T cells. Inhibition of T cells after BVIT also involves decreased induction of the costimulatory molecule ICOS, which, in turn, seems to be dependent on the presence of IL-10, also associated with the inhibited status of T cells after BVIT. Suppression of T cells by IL-10 is an active process, which depends on the expression and participation of CD28. Immune tolerance in specific allergen immunotherapy might be a consequence of decreased Th2 or increased Th1 response of allergen specific T lymphocytes. BVIT shifted cytokine responses to allergen from a TH-2 to a TH-1 dominant pattern, suggesting direct effects on T cells. Many studies showed that severe side effects due to venom immunotherapy are rare. These results suggest that immunological changes after BVIT may be applied to be therapeutic alternative of general allergic diseases including beevenom allergy.

Development of Natural Killer Cells from Hematopoietic Stem Cells

  • Yoon, Suk Ran;Chung, Jin Woong;Choi, Inpyo
    • Molecules and Cells
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    • v.24 no.1
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    • pp.1-8
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    • 2007
  • Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from $CD34^+$hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.

The pathophysiological role of dendritic cell subsets in psoriasis

  • Kim, Tae-Gyun;Kim, Dae Suk;Kim, Hyoung-Pyo;Lee, Min-Geol
    • BMB Reports
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    • v.47 no.2
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    • pp.60-68
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    • 2014
  • Psoriasis is a chronic inflammatory disorder characterized by an erythematous scaly plaque of the skin and is occasionally accompanied by systemic complications. In the psoriatic lesions, an increased number of cytokine-producing dendritic cells and activated T cells are observed, which indicate that psoriasis is a prototype of an immune-mediated dermatosis. During the last decade, emerging studies demonstrate novel roles for the dendritic cell subsets in the process of disease initiation and maintenance of psoriasis. In addition, recently discovered anti-psoriatic therapies, which specifically target inflammatory cytokines produced by lesional dendritic cells, bring much better clinical improvement compared to conventional treatments. These new therapies implicate the crucial importance of dendritic cells in psoriasis pathogenesis. This review will summarize and discuss the dendritic cell subsets of the human skin and their pathophysiological involvement in psoriasis based on mouse- and patient-oriented studies.

A Case of Protein Losing Enteropathy Associated with Henoch-Schönlein Purpura (Henoch-Schönlein 자반증에서 발생된 단백소실장증 1례)

  • Kim, Kee Dae;Oh, Chang Whan;Lee, Eun Young;Kim, Jae Young
    • Clinical and Experimental Pediatrics
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    • v.48 no.2
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    • pp.224-227
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    • 2005
  • Henoch-$Sch{\ddot{o}}nlein$ purpura(HSP) is an IgA mediated immune complex vasculitic disease characterized by non-thrombocytic purpura, arthritis, gastrointestinal manifestations, and glomerulonephritis. HSP related glomerulonephritis induces hypoproteinemia and edema in some cases. Protein-losing enteropathy is another rare but known manifestation of HSP leading to hypoproteinemia and edema. We report a 6-year-old girl with HSP who showed edema caused by intestinal protein loss, evidenced by elevated fecal alpha 1 antitrypsin clearance.

Pneumatosis Coli in a Dog (개의 결장기종 1례)

  • Choi, Ji-Hye;Kim, Tae-Eun;Kim, Hyun-Wook;Seo, Jee-Min;Kim, Mi-Eun;Yoon, Jung-Hee
    • Journal of Veterinary Clinics
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    • v.26 no.3
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    • pp.298-302
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    • 2009
  • A poodle with clinical signs of colorectal disease was diagnosed as pneumatosis coli. In this dog, hypoadrenocorticism and immune-mediated hemolytic anemia concurred. Pneumatosis coli is one of the emphysematous gastrointestinal diseases. The etiology is unknown but mechanical, pulmonary and bacterial theories have been proposed. In pneumatosis coli, gas accumulates within submucosal or subserosal layer of colon or rectum, so intramural radiolucent gas is observed on abdominal radiographs. In this dog, intramural gas accumulation occurred in cecum. Definitive diagnosis was based on radiographic findings and an underlying cause was not elicited. Pneumatosis coli should be included into differential diagnosis for nonspecific colorectal signs.