• 제목/요약/키워드: Immunomodulation

검색결과 185건 처리시간 0.024초

Effects of Artemisia argyi flavonoids on growth performance and immune function in broilers challenged with lipopolysaccharide

  • Yang, Shuo;Zhang, Jing;Jiang, Yang;Xu, Yuan Qing;Jin, Xiao;Yan, Su Mei;Shi, Bin Lin
    • Animal Bioscience
    • /
    • 제34권7호
    • /
    • pp.1169-1180
    • /
    • 2021
  • Objective: This research aimed to study the effects of Artemisia argyi flavonoids (AAF) supplemented in diets on the growth performance and immune function of broiler chickens challenged with lipopolysaccharide (LPS). Methods: A total of one hundred and ninety-two 1-d-old broiler chicks were assigned into 4 treatment groups, which were, respectively, fed a basal diet (control), fed a diet with 750 mg/kg AAF, fed a basal diet, and challenged with LPS, fed a diet with 750 mg/kg AAF, and challenged with LPS. Each treatment had six pens with 8 chicks per pen. On days 14, 16, 18, 20 (stress phase I) and 28, 30, 32, 34 (stress phase II), broilers were injected with LPS (500 ㎍/kg body weight) or an equivalent amount of saline. Results: The results demonstrated that dietary AAF significantly improved the body weight (d 21) and alleviated the decrease of average daily gain in broilers challenged with LPS on d 21 and d 35 (p<0.05). Dietary AAF increased bursa fabricius index, and dramatically attenuated the elevation of spleen index caused by LPS on d 35 (p<0.05). Furthermore, serum interleukin-6 (IL-6) concentration decreased with AAF supplementation on d 21 (p<0.05). Diet treatment and LPS challenge exhibited a significant interaction for the concentration of IL-1β (d 21) and IL-6 (d 35) in serum (p<0.05). Additionally, AAF supplementation mitigated the increase of IL-1β, IL-6 in liver and spleen induced by LPS on d 21 and 35 (p<0.05). This study also showed that AAF supplementation significantly reduced the expression of IL-1β (d 21) and nuclear transcription factor kappa-B p65 (d 21 and 35) in liver (p<0.05), and dietary AAF and LPS treatment exhibited significant interaction for the gene expression of IL-6 (d 21), toll like receptor 4 (d 35) and myeloid differentiation factor 88 (d 35) in spleen (p<0.05). Conclusion: In conclusion, AAF could be used as a potential natural immunomodulator to improve growth performance and alleviate immune stress in broilers challenged with LPS.

중간엽줄기세포(MSC)를 이용한 허혈성 혈관질환 치료를 위한 세포치료제 개발: 기초연구에서 임상연구 (Development of Cell Therapeutics against Ischemic Vascular Diseases Using Mesenchymal Stem Cells: From Bench to Bed)

  • 이은지;박신후;서정호;안효경;남시현;권상모
    • 생명과학회지
    • /
    • 제32권7호
    • /
    • pp.567-577
    • /
    • 2022
  • 최근 인구 고령화로 인해 허혈성 심장질환, 허혈성 뇌졸중, 말초 동맥 질환 등의 허혈성 혈관질환의 유병률이 지속적으로 증가하고 있다. 허혈성 질환에 대한 현재 표준화된 치료법은 약물 요법 및 수술을 통한 재관류요법이다. 재관류요법은 손상된 동맥의 기능을 회복시킬 수 있지만 허혈로 인해 손상된 주변 조직의 기능 회복에 있어 효율적이지 않다. 그러므로 허혈 질병을 안전하고 효과적으로 치료하고 주변 조직의 기능을 회복시킬 수 있는 새로운 치료전략의 개발이 필요하다. 이러한 한계를 극복하기 위해 손상된 부위를 재생하는 줄기세포 기반 치료가 허혈성 혈관질환의 유망한 전략으로 연구되어 왔다. 다양한 조직에서 분리할 수 있는 중간엽줄기세포(MSC)는 면역 조절, 혈관 신생 촉진 및 다양한 관련 인자의 분비를 통해 손상된 조직을 재생함으로써 허혈성 질환의 치료에 유망한 것으로 나타났다. 또한, 줄기세포 치료 효과를 높이기 위해 3D 배양법을 이용하거나 세포 프라이밍(Cell Priming)과 같은 MSC 기능을 강화하여 이식 효율을 높이는 새로운 접근법이 연구되고 있다. 이 논문에서는 MSC를 허혈성 질환 치료에 사용하는 다양한 전략을 제공하고 허혈성 부위에서 MSC의 분화(Differentiation), 증식(Proliferation) 및 생착(Engraftment)과 같은 이식의 문제에 대해 논의한다.

백출 용매추출 방법에 따른 항산화 활성 및 항염증 효과 (Antioxidant and Anti-inflammatory Activities of Atractylodes japonica According to Extract Methods)

  • 오희경
    • 한국응용과학기술학회지
    • /
    • 제38권6호
    • /
    • pp.1543-1552
    • /
    • 2021
  • 백출(Atractylodes japonica)은 국화과(Compositae)에 속하는 다년생 식물로 한국에서 이뇨작용, 수렴작용, 항알러지, 신경보호, 항암, 면역증강 및 위장관 보호효과 등으로 민간요법에서 널리 사용되고 있다. 백출의 열수 및 70% 에탄올 추출물에 대한 DPPH 및 ABTS 자유라디칼 소거능으로 항산화 활성을 측정하였다. 게다가 NO 생성, iNOS와 COX-2 단백질 발현을 웨스턴 블롯으로 측정하였으며, 염증성 사이토카인의 발현을 RT-PCR 방법으로 측정함으로 항염증 효과를 측정하였다. 열수 및 70% 에탄올 추출물들의 항산화 활성은 농도-의존적인 효과를 보였지만, 추출용매에 따른 차이는 나타나지 않았다. 70% 에탄올에 의한 백출 추출물에서 매우 강한 NO 활성 억제효과를 보였다. 백출 열수 및 에탄올 추출물은 NO 생성에 관여하는 iNOS 및 COX-2 단백질의 발현을 현저히 감소시켰다. 열수 및 70% 에탄올 추출물 모두 염증성 사이토카인인 IL-6 및 IL-1b는 현저히 억제시키지만, TNF-α의 발현은 약하게 억제시키는 결과를 얻었다. 본 연구를 통하여 백출 70% 에탄올 추출물이 NO 생성을 현저히 억제하며, 염증성 사이토카인의 발현을 현저히 감소시키는 효과를 보이므로 염증성 질환 치료 및 개선에 널리 사용될 수 있으리라 생각한다.

Promising Therapeutic Effects of Embryonic Stem Cells-Origin Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis Models: Immunomodulatory and Anti-Apoptotic Mechanisms

  • Hanna Lee;Ok-Yi Jeong;Hee Jin Park;Sung-Lim Lee;Eun-yeong Bok;Mingyo Kim;Young Sun Suh;Yun-Hong Cheon;Hyun-Ok Kim;Suhee Kim;Sung Hak Chun;Jung Min Park;Young Jin Lee;Sang-Il Lee
    • IMMUNE NETWORK
    • /
    • 제23권6호
    • /
    • pp.45.1-45.22
    • /
    • 2023
  • Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical's MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue disease-ILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone. Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited anti-apoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

Indigo Naturalis in Inflammatory Bowel Disease: mechanisms of action and insights from clinical trials

  • Hyeonjin Kim;Soohyun Jeong;Sung Wook Kim;Hyung-Jin Kim;Dae Yong Kim;Tae Han Yook;Gabsik Yang
    • 대한약침학회지
    • /
    • 제27권2호
    • /
    • pp.59-69
    • /
    • 2024
  • This study investigates the therapeutic potential of Indigo Naturalis (IN) in treating a Inflammatory Bowel Disease (IBD). The objective is to comprehensively examine the effects and pharmacological mechanisms of IN on IBD, assessing its potential as an novel treatment for IBD. Analysis of 11 selected papers is conducted to understand the effects of IN, focusing on compounds like indirubin, isatin, indigo, and tryptanthrin. This study evaluates their impact on Disease Activity Index (DAI) score, colon length, mucosal damage, and macrophage infiltration in Dextran Sulfate Sodium (DSS)-induced colitis mice. Additionally, It investigate into the anti-inflammatory mechanisms, including Aryl hydrocarbon Receptor (AhR) pathway activation, Nuclear Factor kappa B (NF-κB)/nod-like receptor family pyrin domain containing 3 (NLRP3)/Interleukin 1 beta (IL-1β) inhibition, and modulation of Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MYD88)/NF-κB and Mitogen Activated Protein Kinase (MAPK) pathways. Immunomodulatory effects on T helper 17 (Th17)/regulatory T cell (Treg cell) balance and Glycogen synthase kinase-3 beta (GSK3-β) expression are also explored. Furthermore, the study addresses the role of IN in restoring intestinal microbiota diversity, reducing pathogenic bacteria, and increasing beneficial bacteria. The findings reveal that IN, particularly indirubin and indigo, demonstrates significant improvements in DAI score, colon length, mucosal damage, and macrophage infiltration in DSS-induced colitis mice. The anti-inflammatory effects are attributed to the activation of the AhR pathway, inhibition of inflammatory pathways, and modulation of immune responses. These results exhibit the potential of IN in IBD treatment. Notably, the restoration of intestinal microbiota diversity and balance further supports its efficacy. IN emerges as a promising and effective treatment for IBD, demonstrating anti-inflammatory effects and positive outcomes in preclinical studies. However, potential side effects necessitate further investigation for safe therapeutic development. The study underscores the need for future research to explore a broader range of active ingredients in IN to enhance therapeutic efficacy and safety.

Adipose Tissue-Derived Mesenchymal Stromal Cells from Ex-Morbidly Obese Individuals Instruct Macrophages towards a M2-Like Profile In Vitro

  • Daiana V. Lopes Alves;Cesar Claudio-da-Silva;Marcelo C. A. Souza;Rosa T. Pinho;Wellington Seguins da Silva;Periela S. Sousa-Vasconcelos;Radovan Borojevic;Carmen M. Nogueira;Helio dos S. Dutra;Christina M. Takiya;Danielle C. Bonfim;Maria Isabel D. Rossi
    • International Journal of Stem Cells
    • /
    • 제16권4호
    • /
    • pp.425-437
    • /
    • 2023
  • Obesity, which continues to increase worldwide, was shown to irreversibly impair the differentiation potential and angiogenic properties of adipose tissue mesenchymal stromal cells (ADSCs). Because these cells are intended for regenerative medicine, especially for the treatment of inflammatory conditions, and the effects of obesity on the immunomodulatory properties of ADSCs are not yet clear, here we investigated how ADSCs isolated from former obese subjects (Ex-Ob) would influence macrophage differentiation and polarization, since these cells are the main instructors of inflammatory responses. Analysis of the subcutaneous adipose tissue (SAT) of overweight (OW) and Ex-Ob subjects showed the maintenance of approximately twice as many macrophages in Ex-Ob SAT, contained within the CD68+/FXIII-A- inflammatory pool. Despite it, in vitro, coculture experiments revealed that Ex-Ob ADSCs instructed monocyte differentiation into a M2-like profile, and under inflammatory conditions induced by LPS treatment, inhibited HLA-DR upregulation by resting M0 macrophages, originated a similar percentage of TNF-α+ cells, and inhibited IL-10 secretion, similar to OW-ADSCs and BMSCs, which were used for comparison, as these are the main alternative cell types available for therapeutic purposes. Our results showed that Ex-Ob ADSCs mirrored OW-ADSCs in macrophage education, favoring the M2 immunophenotype and a mixed (M1/M2) secretory response. These results have translational potential, since they provide evidence that ADSCs from both Ex-Ob and OW subjects can be used in regenerative medicine in eligible therapies. Further in vivo studies will be fundamental to validate these observations.

홍삼 부산물이 스트레스에 대한 산란계 생체반응에 미치는 영향 (Effect of Feeding Red Ginseng Marc on Vital Reaction in Laying Hens under Stress Task)

  • 홍준기;봉미희;박준철;문홍길;이상철;이준헌;황성구
    • 한국가금학회지
    • /
    • 제39권1호
    • /
    • pp.63-70
    • /
    • 2012
  • 본 연구는 홍삼박을 산란계 사료에 첨가하여 고온 환경에서의 적응과 면역 개선 효과를 조사하는 것이 목적이며, 이를 위해 면역 증강 효과를 가진 ${\beta}$-glucan 첨가 사료를 양성대조군으로 설정하여 고온 스트레스 후의 생산성 변화, 혈액생화학 조성, LPS에 대한 면역 반응 및 혈액 항산화 활성을 조사하였다. 52주령 ISA Brown 갈색계를 무첨가구(Negative Control; NC), 시판 면역제제 첨가구(Positive Control; PC, ${\beta}$-glucan 25 ppm), 홍삼 부산물 3% 첨가구(RGM; Red Gingeng Marc)로 구분한 후, 처리당 15수(3수${\times}$5반복)로 배치하여 총 11주간 사양 실험을 2하였다. 8주차에 불쾌지수(THI; temperature humidity index)를 76($27^{\circ}C$, 60%)에서 86($34^{\circ}C$, 60%)으로 상승시키고, 24시간 동안 유지한 후 3주간 회복 시간을 가졌으며, 사양 기간이 종료된 후 LPS(Excherichia coli; SIGMA) 접종을 하였다. 8주간의 일반 사양 실험에서 홍삼박은 산란율을 증대시켰으나(P<0.05), 고온 스트레스 자극 후 혈액 생화학 및 생산성 변화에서 홍삼박의 첨가에 의한 효과는 나타내지 않았다. LPS 접종 시 전체적으로 IgM 농도가 감소되지만 홍삼박 첨가구의 경우 면역제제 첨가구와 동일하게 LPS 주입 후 IgM 농도를 대조구보다 높게 유지하는 것으로 관찰되었다(P<0.05). 또한 혈액 내 SOD 유사 활성을 분석한 결과, 홍삼박 첨가구와 면역제제 첨가구 모두 무첨가구보다 높은 항산화 활성을 유지하는 것으로 관찰되었다(P<0.05). 종합해 보면, 홍삼박은 산란계에서 강한 고온 스트레스 자극에 대한 효과는 관찰되지 않았지만 일반환경에서 산란율을 증대시켜 생산성을 개선하는 효과가 있었다. 또한 ${\beta}$-glucan을 함유한 면역제제와 유사 패턴으로 LPS 접종에 대해 IgM 농도를 높게 유지하고, 혈액 내 항산화 활성을 높이는 효과를 나타내었다. 따라서 홍삼박은 산란계 체내 면역 조절 및 항산화 효과를 가져 산란계 건강과 생산성 증진에 긍정적으로 작용할 것으로 사료된다. 또한 고온 스트레스자극 실험 결과는 앞으로 고온 스트레스 관련 연구에서 고온 환경 설정(불쾌지수, 자극시간)에 유용한 자료로 활용될 수 있다고 사료된다.

Photoimmunology -Past, Present and Future-

  • Daynes, Raymond A.;Chung, Hun-Taeg;Roberts, Lee K.
    • 대한미생물학회지
    • /
    • 제21권3호
    • /
    • pp.311-329
    • /
    • 1986
  • The experimental exposure of animals to sources of ultraviolet radiation (UVR) which emit their energy primarily in the UVB region (280-320nm) is known to result in a number of well-described changes in the recipient's immune competence. Two such changes include a depressed capacity to effectively respond immunologically to transplants of syngeneic UVR tumors and a markedly reduced responsiveness to known inducers of delayedtype (DTH) and contact hypersensitivity (CH) reactions. The results of experiments that were designed to elucidate the mechanisms responsible for UVR-induced immunomodulation have implicated: 1) an altered pattern of lymphocyte recirculation, 2) suppressor T cells(Ts), 3) deviations in systemic antigen presenting cell (APC) potential. 4) changes in the production of interleukin-1-like molecules, and 5) the functional inactivation of epidermal Langerhans cells in this process. The exposure of skin to UVR, therefore, causes a number of both local and systemic alterations to the normal host immune system. In spite of this seeming complexity and diversity of responses, our recent studies have established that each of the UVR-mediated changes is probably of equal importance to creating the UVR-induced immunocompromised state. Normal animals were exposed to low dose UVR radiation on their dorsal surfaces under conditions where a $3.0\;cm^2$ area of skin was physically protected from the light energy. Contact sensitization of these animals with DNFB, to either the irradiated or protected back skin, resulted in markedly reduced CH responses. This was observed in spite of a normal responsiveness following the skin sensitization to ventral surfaces of the UVR-exposed animals. Systemic treatment of the low dose UVR recipients with the drug indomethacin (1-3 micrograms/day) during the UVR exposures resulted in a complete reversal of the depressions observed following DNFB sensitization to "protected" dorsal skin while the altered responsiveness found in the group exposed to the skin reactive chemical through directly UVR-exposed sites was maintained. These studies implicate the importance of EC as effective APC in the skin and also suggest that some of the systemic influences caused by UVR exposure involve the production of prostaglandins. This concept was further supported by finding that indomethacin treatment was also capable of totally reversing the systemic depressions in CH responsiveness caused by high dose UVR exposure (30K joules/$m^2$) of mice. Attempts to analyze the cellular mechanisms responsible established that the spleens of all animals which demonstrated altered CH responses, regardless of whether sensitization was through a normal or an irradiated skin site, contained suppressor cells. Interestingly, we also found normal levels of T effector cells in the peripheral lymph nodes of the UVR-exposed mice that were contact sensitized through normal skin. No effector cells were found when skin sensitization took place through irradiated skin sites. In spite of such an apparent paradox, insight into the probable mechanisms responsible for these observations was provided by establishing that UVR exposure of skin results in a striking and dose-dependent blockade of the efferent lymphatic vessels in all peripheral lymph nodes. Therefore, the afferent phases of immune responses can apparently take place normally in UVR exposed animals when antigen is applied to normal skin. The final effector responses, however, appear to be inhibited in the UVR-exposed animals by an apparent block of effector cell mobility. This contrasts with findings in the normal animals. Following contact sensitization, normal animals were also found to simultaneously contain both antigen specific suppressor T cells and lymph node effector cells. However, these normal animals were fully capable of mobilizing their effector cells into the systemic circulation, thereby allowing a localization of these cells to peripheral sites of antigen challenge. Our results suggest that UVR is probably not a significant inducer of suppressor T-cell activity to topically applied antigens. Rather, UVR exposure appears to modify the normal relationship which exists between effector and regulatory immune responses in vivo. It does so by either causing a direct reduction in the skin's APC function, a situation which results in an absence of effector cell generation to antigens applied to UVR-exposed skin sites, inhibiting the capacity of effector cells to gain access to skin sites of antigen challenge or by sequestering the lymphocytes with effector cell potential into the draining peripheral lymph nodes. Each of these situations result in a similar effect on the UVR-exposed host, that being a reduced capacity to elicit a CH response. We hypothesize that altered DTH responses, altered alloresponses, and altered graft-versus-host responses, all of which have been observed in UVR exposed animals, may result from similar mechanisms.

  • PDF

유근피 추출물이 대식세포 면역조절에 미치는 영향 (Immunomodulatory Activity of Water Extract of Ulmus macrocarpa in Macrophages)

  • 권다혜;강혜주;최영현;정경태;이종환;강경화;현숙경;김병우;황혜진
    • 생명과학회지
    • /
    • 제26권1호
    • /
    • pp.50-58
    • /
    • 2016
  • 왕느릅나무(Ulmus macrocarpa)의 껍질을 말린 유근피는 오랫동안 부종, 감염 및 염증 제어의 목적으로 사용되어져 왔음에도 불구하고 잠재적 면역조절 효과에 관해서는 연구가 이루어진 바 없다. 본 연구에서는 전통 약용자원에서 새로운 면역기능 증가 신소재 발굴의 일환으로 유근피 열수 추출물의 면역 조절 효능을 RAW 264.7 대식세포 모델을 이용하여 조사하였다. 이를 위한 대식세포의 활성화 관련 지표로서 NO, TNF-α, IL-1β 및 IL-10의 생성량 변화를 조사하였다. 비록 유근피 추출물이 처리된 RAW 264.7 대식세포에서 IL-1β의 유의적인 유리는 관찰할 수 없었으나, NO, TNF-α 및 IL-10의 생성은 세포독성을 나타내지 않는 범위에서 유근피 추출물 처리 농도 의존적으로 증가되었으며, 이는 또한 iNOS, TNF-α 및 IL-10의 단백질 발현 증가와 연관되어 있었다. 아울러 유근피 추출물은 LPS에 의한 과도한 NO의 생성 억제능도 함유하고 있었으며, 유근피 추출물에 의한 대식세포의 활성화에는 NF-κB와 PI3K/Akt 및 MAPKs 등과 같은 면역 활성을 유도하는 신호전달계의 활성화가 연관되어 있음을 알 수 있었다. 따라서 본 연구의 결과는 유근피 추출물이 대식세포 활성화를 통한 면역 증강제로서의 개발 가능성이 매우 높음을 시사한다.

흑마늘(Black garlic) 추출물이 마우스 비장세포의 Cytokine 생성에 미치는 영향 (Effect of Black Garlic Extract on Cytokine Generation of Mouse Spleen Cells)

  • 서민정;강병원;박정욱;김민정;이혜현;류은주;주우홍;김광혁;정영기
    • 생명과학회지
    • /
    • 제23권1호
    • /
    • pp.63-68
    • /
    • 2013
  • 생리활성물질을 다량함유하고 있는 마늘의 발효산물인 흑마늘의 면역활성을 검증하기 위하여 C57BL6 마우스 비장세포를 이용하여 흑마늘이 비장세포의 활성화에 미치는 영향을 확인하였다. 흑마늘 추출물은 시판되는 남해 흑마늘 액기스를 농축하여 사용하였다. 그 결과 IL-2에서 흑마늘 추출물만 처리한 군에서 생성이 증가하였으며, LPS와 흑마늘 추출물을 함께 처리하였을 때 IL-2와 TNF-${\alpha}$, IFN-${\gamma}$의 생성이 LPS만 처리한 군보다 증가하여 대식세포나 T림프구의 발현에 의해 일어나는 세포성 매개 면역을 활성화를 유도하는 Th1 세포의 발현을 활성화 하였다. 그리고 IL-6는 흑마늘 추출물만 처리하였을 때 후기생성이 증가하였으며, LPS와 흑마늘 추출물을 함께 처리한 경우 LPS만 처리한 군보다 IL-4와 IL-6의 생성이 증가하였다. IL-10은 LPS와 흑마늘 추출물을 함께 처리하였을 때 후기 생성이 감소하였는데, 이는 B 림프구의 활성화에 따른 항체생성 면역을 활성화하며 Th1 세포로부터 유도되는 세포성 면역반응을 억제함으로서 항체유도 체액성 면역반응으로 전환을 효과적으로 조절하는 것을 확인하였다. 따라서 흑마늘 추출물은 마우스 비장세포에서 T 림프구의 활성화에 따른 Th1 세포와 Th2 세포가 활성화되어 면역계의 세포성 면역과 체액성 면역반응을 활성화하여 면역조절에 효과를 나타내는 것으로 사료된다.