• Molecules and Cells
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• 제28권4호
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• pp.365-368
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• 2009

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens and initiating innate immune responses. The stimulation of TLRs by microbial components triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-${\beta}$ (TRIF)-dependent downstream signaling pathways. Isoliquiritigenin (ILG), an active ingredient of Licorice, has been used for centuries to treat many chronic diseases. ILG inhibits the MyD88-dependent pathway by inhibiting the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether ILG inhibits the TRIF-dependent pathway. To evaluate the therapeutic potential of ILG, we examined its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by several agonists. ILG inhibited nuclear factor-${\kappa}B$ and interferon regulatory factor 3 activation induced by lipopolysaccharide or polyinosinic-polycytidylic acid. ILG inhibited the lipopolysaccharide-induced phosphorylation of interferon regulatory factor 3 as well as interferon-inducible genes such as interferon inducible protein-10, and regulated activation of normal T-cell expressed and secreted (RANTES). These results suggest that ILG can modulate TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.

• Journal of Plant Biotechnology
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• 제32권2호
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• pp.73-83
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• 2005

Disease resistance in plants is often controlled by gene-for-gene mechanism in which avirulence (avr) gene products encoding by pathogens are specifically recognized, either directly or indirectly by plant disease resistance (R) gene products and sequential signal transduction pathways activating defense responses are rapidly triggered. As a results, not only exhibit a resistance against invading pathogens but also plants maintain the systemic acquired resistance (SAR) to various other pathogens. This molecular interaction between pathogen and plant is commonly compared to innate immune system of animal. Recent studies arising from molecular characterization of a number of R genes from various plant species that confer resistance to different pathogens and corresponding avr genes from various pathogens resulted in the accumulation of a wealth of knowledge on molecular mechanism of gene-for-gene interaction. Furthermore, new technologies of genomics and proteomics make it possible to monitor the genome-wide gene regulation and protein modification during activation of disease resistance, expanding our ability to understand the plant immune response and develop new crops resistant to biotic stress.

• Biomolecules & Therapeutics
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• 제29권4호
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• pp.353-364
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• 2021

The gastrointestinal (GI) tract is a series of hollow organs that is responsible for the digestion and absorption of ingested foods and the excretion of waste. Any changes in the GI tract can lead to GI disorders. GI disorders are highly prevalent in the population and account for substantial morbidity, mortality, and healthcare utilization. GI disorders can be functional, or organic with structural changes. Functional GI disorders include functional dyspepsia and irritable bowel syndrome. Organic GI disorders include inflammation of the GI tract due to chronic infection, drugs, trauma, and other causes. Recent studies have highlighted a new explanatory mechanism for GI disorders. It has been suggested that autophagy, an intracellular homeostatic mechanism, also plays an important role in the pathogenesis of GI disorders. Autophagy has three primary forms: macroautophagy, microautophagy, and chaperone-mediated autophagy. It may affect intestinal homeostasis, host defense against intestinal pathogens, regulation of the gut microbiota, and innate and adaptive immunity. Drugs targeting autophagy could, therefore, have therapeutic potential for treating GI disorders. In this review, we provide an overview of current understanding regarding the evidence for autophagy in GI diseases and updates on potential treatments, including drugs and complementary and alternative medicines.

• IMMUNE NETWORK
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• 제20권1호
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• pp.6.1-6.20
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• 2020

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8⁺ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

• 생명과학회지
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• 제25권7호
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• pp.833-838
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• 2015

다제약제 내성을 가지는 슈퍼 박테리아, 곰팡이, 바이러스, 기생충 감염은 주요한 건강위협인자들이다. 하지만, 건강위협 상황을 극복하기위해 현재 약제의 대안들중 항생펩타이드를 들 수 있다. 항생펩타이드는 자연계 다양한 종에서 생산된다. 항생펩타이드는 작은 단백질로 어류, 양서류, 파충류, 식물 그리고 동물의 감염으로부터 다세포생명체를 보호하는 선천성 면역에 관여하고 있다. 1980년대 이후로 매년 항생펩타이드의 수가 증가하고 있다. 박테리아, 원생생물, 곰팡이, 식물, 동물로부터 동정된 2,000가지 이상의 항생펩타이드가 항생펩타이드 데이터베이스에 등록되어 있다. 이러한 항생펩타이드의 대부분은 11-50개의 아미노산으로 구성되어 있고 하전상태는 0에서 +7까지이며 소수성은 31-70%를 차지하고 있다. 본 보고는 항생펩타이드를 생물학적 원천, 생물학적 기능, 펩타이드 성질, 공유결합패턴, 3차구조등에 의해 분류하였다. 항생펩타이드의 기능은 항균작용외에 세포주화성과 같은 세포생물학적 활성에도 기능성을 가지고 있다. 더욱이 림프절 스트로마로부터 기원한 fibroblastic reticular cell (FRC)에 염증상황 유도시 항생펩타이드가 발현되는 것을 확인하였다. FRC로부터 유도된 항생펩타이드는 whey acidic protein (WAP) 도메인을 포함하고 있었다. 이것은 단백질 도메인에 의해서도 항생펩타이드를 분류 할 수 있다는 것을 제시한다.

• 대한의생명과학회지
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• 제18권3호
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• pp.201-209
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• 2012

Apoptosis is a physiological programmed cell death process. Tubercle bacilli inhibit apoptosis of alveolar macrophages and phagolysosome fusion. We investigated whether the Bcl-2 family anti-apoptotic member, Bfl-1/A1, plays an important role in the anti-apoptotic process during mycobacterial infection. PMA-treated human monocytoid THP-1 cells were infected with mycobacteria (H37Rv, BCG, and K-strain) at a multiplicity of infection (MOI) of 10 for 0, 1.5, 3, 6, 9, 12, 18, 24, 48, or 72 h. In addition, PMA-treated THP-1 cells were pretreated with specific inhibitors for 45 min before stimulation with mycobacteria at an MOI of 10 for 4 h. After the indicated time, the cells were subject to reverse transcription-polymerase chain reaction (RT-PCR) analysis, and a Bfl-1/A1-specific Western blot was performed. In PMA-differentiated THP-1 cells, the expression level of Bfl-1/A1 mRNA was increased by Mycobacterium tuberculosis (MTB) H37Rv infection. The mRNA level of Bfl-1/A1 peaked 3 h after MTB infection, then declined gradually until 9 h. However, Bfl-1/A1 mRNA induction gradually re-increased from 24 h to 72 h after MTB infection. No difference in Bfl-1/A1 expression was detected following infection with MTB H37Rv, K-strain, or M. bovis BCG. These results were not dependent on mycobacterial virulence. Moreover, mRNA levels of other anti-apoptotic molecules (Mcl-1, Bcl-2, and Bcl-xL) were not increased after MTB H37Rv or K-strain infection. These results suggest that mycobacteria induce the innate immune host defense mechanisms that utilize Bfl-1/A1 molecules at early time points, regardless of virulence.

• 대한한방내과학회지
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• 제27권1호
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• pp.228-236
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• 2006

Objectives : Macrophage has an important innate defense role in the immune system. When we are infected with pathogens, macrophage ingests them through phagocytosis or endocytosis, and then secretes many cytokines, such as IL-1, IL-6 and $TGF{\alpha}$, which are regulators of immune responses. The aim of this study is to determine how Samjunghwan effects the expression of cytokine and other immune-related genes in macrophages. Methods : Cells were treated directly with Samjunghwan and/or LPS at regular intervals. Total RNA of cells was isolated using TRIzol reagent, and the changes in cytokine gene expressions were investigated using RT-PCR, western blot and ELISA. Results : $IL-1{\alpha},\;IL-1{\beta}$ and COX-2 genes were inducibly expressed specifically by Samjunghwan in macrophage. Especially, $IL-1{\beta}$ gene was induced most strongly by treatment with Samjunghwan. Over time, treatment with Samjunghwan showed that the expression levels of $IL-1{\alpha}\;and\;$IL-1{\beta}$ genes increased from 1 to 4h, and then decreased from 4 to ISh. However, the expression level of COX-2 gene increased continuously up to 11h. $IL-1{\alpha},\;IL-1{\beta}$ and COX-2 genes were expressed synergistically by a simultaneous treatment of both Samjunghwan and LPS in macrophages. Secretion levels of translated $IL-1{\beta}$ increased continuously up to 11h. Conclusions : Though this study is only a start in the investigation of the efficasy of Samjunghwan, these results suggest that Samjunghwan has positive effects on immune responses.

• 한국식품과학회지
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• 제41권5호
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• pp.477-482
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• 2009

TLRs는 여러 병원균들이 가지고 있는 PAMPs를 인식해서, 선천성 면역 반응을 유도하는 중요한 역할을 한다. TLR4의 이합체 형성은 신호전달 체계의 활성화와 뒤이어 발생하는 선천성 면역 반응을 유도하기 위해서 최초로 일어나는 반응으로 알려져 있다. 우리가 먹는 식품 중에는 항염증 효과가 있다고 널리 알려져 있는 phytochemicals이 포함되어 있다. 특히 ${\alpha},{\beta}$-unsaturated carbonyl group을 가지고 있는 curcumin, 6-shogaol, 그리고 cinnamaldehyde는 Michael addition 반응에 의해서 LPS에 의해서 유도된 TLR4의 이합체 형성을 억제시켜, 전사요소 NF-${\kappa}B$와 IRF3 활성화 및 그것들에 의해서 조절되는 타깃 유전자들을 억제시킨다. 이러한 결과는 ${\alpha},{\beta}$-unsaturated carbonyl group을 가지고 있는 curcumin, 6-shogaol, 그리고 cinnamaldehyde의 항염증 효능에 대한 새로운 기전을 설명해 주는 것이라 할 수 있겠다.

• 한국임상수의학회지
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• 제28권1호
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• pp.113-121
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• 2011

Foot-and-mouth disease (FMD) is a severe vesicular disease of cloven-hoofed animals including domesticated ruminants and pigs. Acute clinical signs may be mild in sheep and goats but are associated with lameness in pigs and mouth lesions with vesicles in cattle. The required condition for a successful pathogen appears to be the ability to counteract both the host innate and adaptive immune response. FMD virus (FMDV) inhibits the induction of antiviral molecules and interferes with the secretory pathway in the infected cell. The surface expression of Major Histocompatibility Complex (MHC) class I molecules is reduced in infected cells. Thus, the ability of the host to recognize and eliminate virus infected cells is decreased. Furthermore, FMDV infection results in a rapid, but transient lymphopenia, reducing the number of T and B cells, and affecting T cell function. The virus appears to premature apoptosis-mediated cell death because it has a very short replication cycle and is able to rapidly produce large amounts of virus. FMDV engages the host protective response at multiple steps to ensure its effective replication and pathogenesis. This review describes the recent pathological and immunological studies to overcome the powerful abilities of FMDV to counteract defense mechanism of host.

• International Journal of Oral Biology
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• 제40권1호
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• pp.11-17
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• 2015

The gingival epithelium of the oral cavity is constantly exposed to exogenous stimuli such as bacterial toxins, allergens, and thermal changes. These exogenous stimuli are resisted by innate host defense in gingival epithelial cells. However, it is unclear exactly how the exogenous stimuli affect detrimentally on the human gingival epithelial cells. Here, we investigated whether the allergen, such as house dust mite (HDM) extract, is linked to $Ca^{2+}$ signaling and proinflammatory cytokine expression in primary cultured human gingival epithelial cells. HDM extract induced an increase in intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in a dose-dependent manner. Extracellular $Ca^{2+}$ depletion did not affected on the HDM extract-induced increase in $[Ca^{2+}]_i$. The HDM extract-induced increase in $[Ca^{2+}]_i$ was abolished by the treatment with U73122 and 2-APB, which are inhibitors of phospholipase C (PLC) and inositol 1,4,5-trisphosphate ($IP_3$) receptor. Moreover, HDM extract induced the mRNA expression of pro-inflammatory cytokine, interleukin (IL)-8. These results suggest that HDM extract triggers $PLC/IP_3$-dependent $Ca^{2+}$ signaling and IL-8 mRNA expression in primary cultured human gingival epithelial cells.