• Molecules and Cells
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• 제44권5호
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• pp.356-362
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• 2021

An increasing number of studies have revealed an interaction between gut microbiota and tumors. The enrichment of specific bacteria strains in the intestines has been found to modulate tumor growth and influence the mechanisms of tumor treatment. Various bacteria are involved in modulating the effects of chemotherapeutic drugs currently used to treat patients with cancer, and they affect not only gastrointestinal tract tumors but also distant organ tumors. In addition, changes in the gut microbiota are known to be involved in the antitumor immune response as well as the modulation of the intestinal immune system. As a result, the gut microbiota plays an important role in modulating the efficacy of immune checkpoint inhibitors. Therefore, gut microbiota could be considered as an adjuvant treatment option with other cancer treatment or as another marker for predicting treatment response. In this review, we examine how gut microbiota affects cancer treatments.

• Molecules and Cells
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• 제43권3호
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• pp.251-263
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• 2020

Flagellin, a major structural protein of the flagellum found in all motile bacteria, activates the TLR5- or NLRC4 inflammasome-dependent signaling pathway to induce innate immune responses. Flagellin can also serve as a specific antigen for the adaptive immune system and stimulate anti-flagellin antibody responses. Failure to recognize commensal-derived flagellin in TLR5-deficient mice leads to the reduction in anti-flagellin IgA antibodies at steady state and causes microbial dysbiosis and mucosal barrier breach by flagellated bacteria to promote chronic intestinal inflammation. Despite the important role of anti-flagellin antibodies in maintaining the intestinal homeostasis, regulatory mechanisms underlying the flagellin-specific antibody responses are not well understood. In this study, we show that flagellin induces interferon-β (IFN-β) production and subsequently activates type I IFN receptor signaling in a TLR5- and MyD88-dependent manner in vitro and in vivo. Internalization of TLR5 from the plasma membrane to the acidic environment of endolysosomes was required for the production of IFN-β, but not for other pro-inflammatory cytokines. In addition, we found that anti-flagellin IgG2c and IgA responses were severely impaired in interferon-alpha receptor 1 (IFNAR1)-deficient mice, suggesting that IFN-β produced by the flagellin stimulation regulates anti-flagellin antibody class switching. Our findings shed a new light on the regulation of flagellin-mediated immune activation and may help find new strategies to promote the intestinal health and develop mucosal vaccines.

• Journal of Radiation Protection and Research
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• 제45권4호
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• pp.163-170
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• 2020

Background: Gut microflora contributes to the nutritional metabolism of the host and to strengthen its immune system. However, if the intestinal barrier function of the living body is destroyed by radiation exposure, the intestinal bacteria harm the health of the host and cause sepsis. Therefore, this study aims to trace short-term radiation-induced changes in the mouse gut microflora-dominant bacterial genus, and analyze the degree of intestinal epithelial damage. Materials and Methods: Mice were irradiated with 0, 2, 4, 8 Gy X-rays, and the gut microflora and intestinal epithelial changes were analyzed 72 hours later. Five representative genera of Actinobacteria, Firmicutes, and Bacteroidetes were analyzed in fecal samples, and the intestine was pathologically analyzed by Hematoxylin-Eosin and Alcian blue staining. In addition, DNA fragmentation was evaluated by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Results and Discussion: The small intestine showed shortened villi and reduced number of goblet cells upon 8 Gy irradiation. The large intestine epithelium showed no significant morphological changes, but the number of goblet cells were reduced in a radiation dose-dependent manner. Moreover, the small intestinal epithelium of 8 Gy-irradiated mice showed significant DNA damaged, whereas the large intestine epithelium was damaged in a dose-dependent manner. Overall, the large intestine epithelium showed less recovery potential upon radiation exposure than the small intestinal epithelium. Analysis of the intestinal flora revealed fluctuations in lactic acid bacteria excretion after irradiation regardless of the morphological changes of intestinal epithelium. Altogether, it became clear that radiation exposure could cause an immediate change of their excretion. Conclusion: This study revealed changes in the intestinal epithelium and intestinal microbiota that may pave the way for the identification of novel biomarkers of radiation-induced gastrointestinal disorders and develop new therapeutic strategies to treat patients with acute radiation syndrome.

• Journal of Plant Biotechnology
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• 제37권3호
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• pp.283-291
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• 2010

Vaccine is one of the best known and most successful applications of immunological theory to human health and it protects human life through inducing the immune response in systemic compartment. However, when we consider the fact that mucosal epithelium is exposed to diverse foreign materials including viruses, bacteria, and food antigens and protects body from entry of unwanted materials using layer of tightly joined epithelial cells, establishing the immunological barrier on the lining of mucosal surfaces is believed to be an effective strategy to protect body from unwanted antigens. Unfortunately, however, oral mucosal site, which is considered as the best target to induce mucosal immune response due to application convenience, is prone to induce immune tolerance rather than immune stimulation. Since intestinal epithelium is tightly organized, a prerequisite for successful mucosal vaccination is delivery of antigen to mucosal immune induction site including a complex system of highly specialized cells such as M cells. Consequently, development of efficient mucosal adjuvant capable of introducing antigens to mucosal immune induction site and overcome oral tolerance is an important subject in oral vaccine development. In this review, various approaches on the development of oral mucosal adjuvants being suggested for effective oral mucosal immune induction.

• 생명과학회지
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• 제23권3호
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• pp.448-461
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• 2013

크론병과 궤양성 대장염으로 잘 알려져 있는 염증성 장질환은 재발과 호전을 반복하는 만성적인 염증 및 이에 따른 합병증을 특징으로 하는 원인 불명의 질환이다. 염증성 장질환의 발생 원인은 아직 명확히 알려져 있지 않지만 흡연이나 식이와 같은 환경적 요인, 장내 세균총과 같은 미생물학적 요인, 면역 매개에 의한 조직 손상과 같은 면역학적 요인 그리고 유전학적 요인 등이 복합적으로 발생기전에 관여 할 것이라고 추정한다. 특히 사이토카인과 같은 염증매개물질에 의해 세포매개염증반응의 일련의 과정이 유발 혹은 증폭되거나, 면역 조절 기능의 면화로 장 점막의 국소적 조직 손상을 유발하게 되며 면역 및 염증 반응이 적절하게 감소되지 않고 지속되어 만성 염증에 이르게 된다. 최근 이러한 염증반응에 중요한 역할을 담당하는 사이토카인 유전자에 관심이 몰리고 있다. 사이토카인은 활성화된 면역세포에서 주로 생성되는 당단백으로서 분자량이 8~10 kD 정도이며, 면역 반응시 T세포, B세포, 대식세포 등의 면역세포 상호간에 활성화, 증식 및 분화 등에 관계하여 국소적 조직 손상 및 염증반응을 일으킨다. 반면에 장의 구조와 기능에 있어 중요한 기질인 식이 섬유소에서 유래되는 Butyrate는 친염증성 사이토카인을 감소시키고 항염증성 사이토카인을 증가시킴으로써 장관 면역계에 대한 조절기능을 보이고 있다. 따라서 본 총설에서는 Butyrate의 항염증 효과에 대한 분자적 기작을 면역세포에서 Butyrate가 가지는 사이토카인 조절 능력을 통해 이해하고 Butyrate가 염증성 장질환에 대해 새로운 치료 전략을 제시 해 줄 것으로 기대한다.

• 한국약용작물학회지
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• 제22권4호
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• pp.276-288
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• 2014

The six polysaccharide fractions were prepared by chromatographic procedure from the hot water extracts of the aboveground parts of Astragalus membranaceus. These six polysaccharides from aboveground parts of Astragalus membranaceus Bunge were tested for gut-mucosal immune activity and acute toxicity. In a view of molecular weight, the six fractions were estimated to be 75000, 88000, 129000 and 345000 Da, respectively. Component sugar analysis indicated that these fractions were mainly consisted of galactose (46.3 ~ 11.8%) and arabinose (35.4 ~ 9.9%) in addition to glucose, rhamnose, fucose, arabinose, xylose, mannose, glucuronic acid and galacturonic acid. Among the six major purified polysaccharides, AMA-1-b-PS2 showed highest bone merrow cell proliferation and lymphocyte of Peyer's patch stimulating activity. It may be concluded that intestinal immune system modulating activity of aboveground parts from Astragalus membranaceus Bunge is caused by polysaccharides having a polygalacturonan moiety with neutral sugars such as arabinose and galactose. In single oral dose toxicity study, no differences were observed between control and treated groups in clinical signs. The results indicated that lethal dose 50 ($LD_{50}$) of water extracts from Astragalus membranaceus-aboveground parts was found to be higher than 5000 mg/kg/day in this experiment. From the above results, we may suggest that Astragalus membranaceus-aboveground parts might have useful as a safe material for functional food and pharmaceutics.

• 한국식품영양과학회지
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• 제33권9호
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• pp.1476-1485
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• 2004

90여종의 전통차 및 죽류용 식물로부터 조제된 다양한 용매추출물 중에서, 귤피(peels of C. unshiu)의 냉수추출물 (CUI-0)이 Peyer’s patch를 매개로 한 가장 높은 장관면역 활성을 나타내었으며 다시마(L. japonica), 둥글레(P. japonicum), 탱자(P. trifoliata)의 냉수추출물과 구기자(L. chinense) 및 치자(G. jasminoides)의 열수추출물을 제외한 나머지 식물의 용매추출물은 거의 활성을 가지지 못하였다. CUI-0는 MeOH-가용성 획분(CUI-1), MeOH-불가용성이면서 EtOH-가용성 획분(CUI-2)과 조다당 획분(CUI-3)으로 분획되었다. 이러한 획분들 중 CUI-3은 Peyer’s patch 세포를 매개로 하는 골수세포 증식의 자극활성이 가장 높았으며 arabinose, galacturonic acid, galactose, glucose, glucuronic acid와 rhmanose(molar ratio; 1.00:0.53:0.45:0.28:0.28:0.19) 등을 주요 구성당으로 함유하고 있었으며 소량의 단백질(9.4%)도 구성물질로 포함된 활성 획분임이 밝혀졌다. CUI-3의 장관면역 활성은 pronase 및 periodate 처리에 의해 감소되었으며 특히 periodate 산화는 CUI-3의 활성에 심각한 영향을 끼치는 것을 알 수 있었다. 활성 획분으로서 당 함량이 높은 CUI-3IIb-3-2는 DEAE-Sepharose FF, Sepharose CL-6B 및 Sephacryl S-200에 의해 귤피 냉수추출물의 조다당 획분으로부터 정제되었으며 HPLC에 의해 분자량 약 18,000 Da의 단일 peak임을 확인하였다. CUI-3IIb-3-2는 주로 arabinose, galactose, rhamnose, galacturonic acid와 glucuronic acid(molar ratio; 1.00:0.54:0.28:1.45:0.63) 등의 구성당으로 구성되어져 있었으며 소량의 단백질(3.2%)이 함유되어진 물질로 구성되어 있었다. 한편 CUI- 3IIb-3-2는 Peyer’s patch를 경유하였을 때만 골수세포 증식활성을 나타내었으며 활성물질 자체가 직접 골수세포 증식활성에 관여하지는 않는것으로 확인되었다. 이러한 결과로부터 귤피의 장관면역 활성은 측쇄에 arabinose와 galactose 등의 중성당이 결합된 polygalacturonan 구조를 갖는 펙틴계통의 다당류에 기인하고 있음을 보여주었다.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.449-457
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• 2015

The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents.

• IMMUNE NETWORK
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• 제22권2호
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• pp.16.1-16.20
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• 2022

The gastrointestinal tract is the first organ directly affected by fasting. However, little is known about how fasting influences the intestinal immune system. Intestinal dendritic cells (DCs) capture antigens, migrate to secondary lymphoid organs, and provoke adaptive immune responses. We evaluated the changes of intestinal DCs in mice with short-term fasting and their effects on protective immunity against Listeria monocytogenes (LM). Fasting induced an increased number of CD103⁺CD11b^- DCs in both small intestinal lamina propria (SILP) and mesenteric lymph nodes (mLN). The SILP CD103⁺CD11b^- DCs showed proliferation and migration, coincident with increased levels of GM-CSF and C-C chemokine receptor type 7, respectively. At 24 h post-infection with LM, there was a significant reduction in the bacterial burden in the spleen, liver, and mLN of the short-term-fasted mice compared to those fed ad libitum. Also, short-term-fasted mice showed increased survival after LM infection compared with ad libitum-fed mice. It could be that significantly high TGF-β2 and Aldh1a2 expression in CD103⁺CD11b^- DCs in mice infected with LM might affect to increase of Foxp3⁺ regulatory T cells. Changes of major subset of DCs from CD103⁺ to CD103^- may induce the increase of IFN-γ-producing cells with forming Th1-biased environment. Therefore, the short-term fasting affects protection against LM infection by changing major subset of intestinal DCs from tolerogenic to Th1 immunogenic.

• 대한한의학원전학회지
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• 제26권4호
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• pp.105-116
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• 2013

Objective : If the penetration ratio of the intestinal mucosa is increased, the toxic or unhealthy materials - which should not be absorbed into our bodies - will be come into our bodies. They cause a sort of anti-toxic response or confusion of the immune system, and ultimately bring various types of diseases. This syndrome is related "Poison in Excrement" or "Internal Damage(內傷發癍)" and Leaky Gut Syndrome, so I will study on the relationship between them. Method : Study on the relationship between Dae-Jang-Jung-gyeok and Leaky Gut Syndrome. Result : Korean doctors in ancient times called this syndrome "Poison in Excrement" or "Internal Damage(內傷發癍)" and treated it with "Dae-Jang-Jung-Gyeok(大腸正格)". Leaky Gut Syndrome is a sort of clinical lesion, which allows foreign and harmful toxins in and results in a disorder of the immune system due to the leaking intestinal mucosa. Conclusion : Based upon the analyses, Dae-Jang-Jung-Gyeok and Leaky Gut Syndrome are closely related. Therefore diseases caused by the Leaky Gut Syndrome might be expected to be cured by Dae-Jang-Jung-Gyeok. Particularly the use of treatments for self-immune diseases and allergic diseases such as atopyic dermatitis and articular rheumatism should be expected to reveal a new path of treatment for other disorders such as Leaky Gut Syndrome.