Inflammatory Bowel Disease and Cytokine

Eun Young Choi(최은영),Kwang Keun Cho(조광근),In Soon Choi(최인순) 한국생명과학회 2013 생명과학회지 Vol.23 No.3

크론병과 궤양성 대장염으로 잘 알려져 있는 염증성 장질환은 재발과 호전을 반복하는 만성적인 염증 및 이에따른 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. Inflammatory bowel disease, known as Crohn’s disease and ulcerative colitis, is an unexplained disease characterized by chronic inflammation that repeats a cycle of relapse, improvement, and complications. The cause of inflammatory bowel disease is not clearly known, but it is predicted that a complex of various factors precipitate its occurrence. In particular, inflammatory mediators, such as cytokine, induce an increase in cell-mediated inflammatory responses. Focal tissue damage then occurs in the intestinal mucosa because of the weakening of the immune-modulating functions of cotton. Immune and inflammatory responses do not decrease appropriately but continue until they lead to chronic inflammation. Current research has focused on the cytokine genes, which have important roles in these inflammatory responses. Cytokine is a glycoprotein that is produced mostly in activated immune cells. It connects the activation, multiplication, and differentiation between immune cells, which causes focal tissue damage and inflammatory response. Moreover, butyrate, which originates in dietary fiber and plays an important role in the structure and function of the intestinal area, shows control functions in the intestinal immune system by decreasing the proinflammatory cytokine and increasing the anti-inflammatory cytokine. Therefore, this research investigated the molecular mechanism of the anti-inflammatory effects of butyrate to comprehend the cytokine controlling abilities of butyrate in the immune cells. Butyrate is expected to have potential in new treatment strategies for inflammatory bowel disease.

Anti-inflammatory effect of Chunkoongkeigi-tang on IL-1β- induced inflamed A549 by the inhibition of COX-2 expression

Eun-Jin An,김관일,권대호,Hyeung-Jin Jang 대한독성 유전단백체 학회 2019 Molecular & cellular toxicology Vol.15 No.1

Backgrounds: Inflammatory lung disease can arise due to the immoderate expression of pro-inflammatory genes and the disharmony of complex cytokines. Chunkoongkeigi-tang (CKT) has been prescribed to patients with asthmatic symptoms in herbal medicine clinics. However, the effects of CKT on the inflamed human lung cell line A549 have yet to be revealed. Thus we investigate whether CKT can suppress inflammatory response on interleukin 1β (IL-1β)-induced inflamed A549. Methods: In an effort to understand the inhibitory activity of CKT on inflamed A549, we use IL-1β to induce inflammatory gene COX-2 expressions on A549. Inhibition of COX-2 expression and inflammatory cytokine secretion through blocking mitogen activated protein kinase (MAPK) pathway and transcriptional nuclear factor kappa B (NF-κB) activity was confimed by western blot and real-time PCR. Compounds in CKT were identified by liquid chromatography-mass spectrometry (LC-MS). Results: CKT inhibited increased COX-2 in an IL-1β- induced inflammatory state of A549. We confirmed that CKT regulated the mitogen activated protein kinase (MAPK) pathway and transcriptional nuclear factor kappa B (NF-κB). Additionally, a suppressive effect of CKT on the mRNA expression levels of cytokine- related asthma ((IL-5, IL-6, IL-17 and TNF-α) was noted in IL-1β-induced inflamed A549. According to LC-MS analysis, we identified several components in CKT which can be expected to be the active compounds of the anti-inflammatory effect of CKT. Conclusion: We verify the anti-inflammatory effect of CKT via the reduction of the IL-1β-induced increased COX-2 expression through the MAPK and NF-κB pathways, suggesting useful anti-asthmatic potential by inhibiting inflammatory cytokines, especially in patients with asthma.

Role of Salvia miltiorrhiza for Modulation of Th2-derived Cytokines in the Resolution of Inflammation

문선희,김경제,신슬미,김설아,오희은,한신하,이승정 대한면역학회 2011 Immune Network Vol.11 No.5

Background: Salvia miltiorrhiza (SM) has been used to treat inflammatory diseases including edema and arthritis; however,the anti-inflammatory mechanism of SM action remains unresolved. Methods: The effects of an ethanol extract of SM (ESM) on pro-inflammatory cytokines such as TNF-α,IL-1β, IL-6, and NO, and on anti-inflammatory cytokines including IL-4, IL-10, TGF-β, and IL-1Ra have been studied in an attempt to elucidate the anti-inflammatory mechanism in murine macrophages. Results: ESM inhibited the production of pro-inflammatory cytokines via down-regulation of gene and protein expression whereas it increased the anti-inflammatory cytokines. Furthermore, ESM inhibited the expression of the chemokines, RANTES and CX3CL1, as well as of inflammatory mediators such as TLR-4 and 11β-HSD1. Conclusion: These results indicated that the regulatory effects of ESM may be mediated though the suppression of pro-inflammatory cytokines as well as the induction of anti-inflammatory cytokines. Consequently, we speculate that ESM has therapeutic potential for inflammation-associated disorders.

Role of Salvia miltiorrhiza for Modulation of Th2-derived Cytokines in the Resolution of Inflammation

Moon, Sun-Hee,Shin, Seul-Mee,Kim, Seul-Ah,Oh, Hee-Eun,Han, Shin-Ha,Lee, Seung-Jeong,Kim, Kyung-Jae The Korean Association of Immunobiologists 2011 Immune Network Vol.11 No.5

Background: Salvia miltiorrhiza (SM) has been used to treat inflammatory diseases including edema and arthritis; however, the anti-inflammatory mechanism of SM action remains unresolved. Methods: The effects of an ethanol extract of SM (ESM) on pro-inflammatory cytokines such as TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and NO, and on anti-inflammatory cytokines including IL-4, IL-10, TGF-${\beta}$, and IL-1Ra have been studied in an attempt to elucidate the anti-inflammatory mechanism in murine macrophages. Results: ESM inhibited the production of pro-inflammatory cytokines via down-regulation of gene and protein expression whereas it increased the anti-inflammatory cytokines. Furthermore, ESM inhibited the expression of the chemokines, RANTES and CX3CL1, as well as of inflammatory mediators such as TLR-4 and $11{\beta}$-HSD1. Conclusion: These results indicated that the regulatory effects of ESM may be mediated though the suppression of pro-inflammatory cytokines as well as the induction of anti-inflammatory cytokines. Consequently, we speculate that ESM has therapeutic potential for inflammation-associated disorders.

2시간 허혈 후 재관류 시점에 따른 흰쥐의 혈청 및 장딴지근의 친염증성 사이토카인 및 항염증성 사이토카인의 변화

김신영(Shin-Young Kim) 대한체질인류학회 2014 해부·생물인류학 (Anat Biol Anthropol) Vol.27 No.2

본 연구는 허혈 후 재관류 시점에 따라 혈청과 뼈대근육에서 나타나는 친염증성 및 항염증성 사이토카인(pro- and anti-inflammatory cytokine)의 변화 양상을 비교 분석하여 뼈대근육의 허혈 후 재관류 시점에 따라 나타나는 염증성 반응의 변화와 이를 대표할 수 있는 표지인자를 확인하는 데 목적이 있다. 실험동물은 12주령 ICR계 수컷 생쥐를 사용하여 대조군과 허혈 후 재관류 시간에 따라 재관류 0, 0.5, 1, 2, 4, 8, 16, 24시간군으로 분류하였고, 허혈 처치는 왼온엉덩동맥(left common iliac artery)을 2시간 동안 혈관집게로 차단하였다. 재관류 시간경과에 맞추어 실험동물을 마취시킨 후 심장의 오른 심방에서 채취한 혈액의 혈청과 장딴지근 조직액에서 친염증성 사이토카인 (Eotaxin, IFNγ, IL-1α, IL-1β, IL-2, IL-3, IL-5, IL-6, MCP-1, MDC, MIP-1α, RANTES, TARC, TCA-3)과 항염증성 사이토카인(IL-4, IL-10)의 변화를 확인하기 위하여 ELISA 분석을 시행하였다. 연구결과 허혈 후 재관류 시점에 따른 친염증성 사이토카인의 발현은 뼈대근육 내 재관류 0시간군에서, 혈청에서는 대조군과 재관류 0, 1, 2, 4, 8, 16시간군에서 사이토카인들 사이의 발현양의 차이가 유의한 것으로 관찰되었고(p?.05), 항염증성 사이토카인의 발현은 혈청 내 재관류 4시간군에서 사이토카인들 사이의 발현양의 차이가 유의한 것으로 관찰되었다(p?.05). 또한 대조군과 비교하여 유의한 차이를 보이는 재관류 시간은 친염증성 사이토카인에서는 혈청 내 재관류 2, 4, 16시간군이었고, 항염증성 사이토카인에서는 혈청 내 재관류 4시간군이었다(p?.05). 본 연구를 토대로 허혈 후 사이토카인들의 변화 양상은 재관류 시점에 따라 뼈대근육보다는 혈청에서 발현양의 차이가 유의하게 나타났으며, 특히 혈청에서 재관류 4시간군에 관찰되는 IL-6와 재관류 16시간군에 관찰되는 MCP-1은 다른 사이토카인보다 유의하게 높은 농도를 보임에 따라 친염증성 사이토카인을 대표하는 표지인자가 될 수 있을 것으로 사료된다. This study aimed to investigate the inflammatory changes and their main indicators according to the time-period of postischemic reperfusion injury confirmed by analyzing changes of both pro-inflammatory and anti-inflammatory cytokines in the skeletal muscle and serum. By using 12-week-old male ICR strain mice were grouped into sham control and 8 different time-periods of reperfusion groups (0, 0.5, 1, 2, 4, 8, 16, 24 hours). Left common iliac artery of each mice in the reperfusion group was devascularized by a vascular clamp for 2 hours. Once anesthesia was applied to the experimental animals, blood serum was obtained from right heart atrium on the difference time-period of reperfusion (0-, 0.5-, 1-, 2-, 4-, 8-hour, respectively). Then, tissue fluid was collected in calf muscles (gastrocnemius muscle) after the mice were sacrificed by cervical dislocation. By using these serum and tissue fluids, enzyme-linked immunosorbent assay (ELISA) was used to analyze both pro-inflammatory cytokines (Eotaxin, IFNγ, IL-1α, IL-1β, IL-2, IL-3, IL-5, IL- 6, MCP-1, MDC, MIP-1α, RANTES, TARC, TCA-3) and anti-inflammatory cytokines (IL-4, IL-10). Consequently, there were significant differences of pro-inflammatory cytokines levels in the skeletal muscle of 0- hour reperfusion group (p?.05) and those in the serum of 0-, 1-, 2-, 4-, 8-, 16-hour reperfusion groups (p?.05). In the serum of 4-hour reperfusion group, the presence of anti-iflammatory cytokines was significant from other groups (p?.05). By the comparison with the control group, furthermore, pro-inflammatory cytokines in the serum of 2-, 4-, 16-hour reperfusion group and anti-inflammatory cytokines in the serum of 4-hour reperfusion group were considerably different (p?.05). To sum up, changes of cytokine levels according to the time-period of reperfusion were considerably different in the serum rather than the tissue fluids from the skeletal muscle. In particular, IL-6 and MCP-1 in the serum showed higher density in 4- and 16-hour reperfusion groups so that they could be considered as the main indicator of pro-inflammatory cytokines.

Pro-inflammatory Cytokine Production Inhibitory Effects of Broccoli extract

Jeong-Sook Park ASCONS 2021 IJBSA Vol.3 No.1

Background/Objectives: This study aims to demonstrate pro-inflammatory cytokine production inhibitory effects using broccoli extract. Methods/Statistical analysis: Thus, This paper was carried out to see the production of NO and pro-inflammatory cytokine ,TNF-α and IL-6 using the macrophages of LPS-treated mice. The cytotoxicity test was used 96 AQueous One solution cell proliferation assay. NO was measured using NO Detection Kit, and the production of pro-inflammatory cytokine was measured using ELISA kit. Findings: As a result, broccoli extract had no cytotoxicity at 10ug/mL to 1,000 ug/mL and significantly inhibited the production of NO as well as TNF-α and IL-6 which are pro-inflammatory cytokines. In the RAW 264.7 macrpphage cells, Pro-inflammatory cytokine production inhibitory effects are likely to be diversely utilized as basic physiological activity data and functional materials to demonstrate anti-inflammatory properties of broccoli extract.Improvements/Applications: In conclusion, this study can be used to a basic data to objectively demonstrate the physiological activity of immunological mechanism associated with the anti-inflammatory action of broccoli extract. However, in-depth research on anti-inflammatory is needed.

Propionibacterium acnes에 의한 염증반응에서 Eurya persicifolia Gagnep. 추출물의 억제효과

신진학,서수련,Shin, Jin Hak,Seo, Su Ryeon 한국미생물학회 2019 미생물학회지 Vol.55 No.3

여드름은 일반적인 피부 염증성 질환으로 알려져 있다. 여드름은 모낭 내 피지선에서 나타나는 만성 염증 질환이다. Propionibacterium acnes (P. acnes)의 증식은 대식세포가 염증성 사이토카인을 분비하도록 자극한다. 최근 연구에서 여러 천연 추출물이 P. acnes에 의해 매개되는 염증반응을 감소시키는 것을 확인하였다. 그러나 P. acnes에 의한 염증반응에서 E. persicifolia Gagnep. (E. persicifolia) 추출물의 억제효과에 관한 연구는 수행되지 않았다. 따라서 본 연구에서는 P. acnes에 의해 유도된 염증 반응에서 E. persicifolia 추출물의 항 염증효과를 조사하였다. P. persicifolia 추출물은 마우스 대식세포주인 RAW 264.7에서 P. acnes에 의해 유도된 IL-$1{\beta}$, IL-6, TNF-${\alpha}$ 및 iNOS와 같은 염증 매개체의 발현 수준을 억제하였다. 또한 E. persicifolia 추출물이 염증성 사이토카인 발현의 주요 조절인자인 NF-${\kappa}B$ 전사 활성화를 억제한다는 것을 발견했다. 본 연구 결과는 P. acnes의 치료를 위한 잠재적인 치료물질로서 E. persicifolia 추출물을 제안한다. Acne is a chronic inflammatory disease outbreak in the sebaceous glands within the hair follicle. The proliferation of Propionibacterium acnes (P. acnes) causes monocytes to stimulate secretion of inflammatory cytokines. A number of studies proposed the inhibitory effects of P. acnes-mediated inflammation by several natural extracts. However, studies on the effect of Eurya persicifolia Gagnep. (E. persicifolia) extracts on the inflammatory responses by P. acnes have not been explored yet. In this study, we investigated the anti-inflammatory effect of E. persicifolia extract in the inflammatory reactions induced by P. acnes. We found that E. persicifolia extract successfully diminished the expression levels of inflammatory mediators such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and iNOS in P. acnes-activated mouse macrophage RAW 264.7 cells. We found that the immunosuppressive effect of E. persicifolia extract in the P. acnes-activated inflammatory signaling is mediated by the regulation of NF-${\kappa}B$ transcriptional activation, which is a key regulator of inflammatory cytokine expression. Our results suggest that E. persicifolia extract held potentials for the treatment of P. acnes by suppressing NF-${\kappa}B$ signaling pathways.

Pro-inflammatory Cytokine Production Inhibitory Effects of Burdock extract

Jeong-Sook Park ASCONS 2021 IJBSA Vol.3 No.4

Background/Objectives: This study aims to demonstrate pro-inflammatory cytokine production inhibitory effects using Burdock extract. In addition, the basic mechanism of the anti-inflammatory mechanism of burdock is to be studied Methods/Statistical analysis: Thus, This paper was carried out to see the production of NO and pro-inflammatory cytokine ,TNF-α, IL-6 and IL-8 using the macrophages of LPS-treated mice. The cytotoxicity test was used 96 AQueous One solution cell proliferation assay. NO was measured using NO Detection Kit, and the production of pro-inflammatory cytokine was measured using ELISA kit. Findings: As a result, Burdock extract had no cytotoxicity at 10ug/mL to 1,000 ug/mL and significantly inhibited the production of TNF-α as well as IL-6 and IL-8 which are pro-inflammatory cytokines. In the RAW 264.7 macrophage cells, Pro-inflammatory cytokine production inhibitory effects are likely to be diversely utilized as basic physiological activity data and functional materials to demonstrate anti-inflammatory properties of broccoli extract. Improvements/Applications: In conclusion, this study can be used to a basic data to objectively demonstrate the physiological activity of immunological mechanism associated with the anti-inflammatory action of Burdock extract. However, in-depth research on anti-inflammatory is needed.

위령탕 혼합단미연조엑스의 항염증 효과

김명진,김세진,남원희,임현희,전영희,손수미,김정옥 대한한의학방제학회 2020 大韓韓醫學方劑學會誌 Vol.28 No.4

Objectives : Wiryeong-tang (WRT) is a traditional herbal medicine used to treat kidney-related diseases. However, the anti-inflammatory and anti-gastritis effect of Wiryeong-tang was not well known. Therefore, we experimented to confirmed the anti-inflammatory and anti-gastritis effects of Wiryeong-tang. Methods : The RAW 264.7 cells were pre treated with Wiryeong-tang mix soft extract (WRT-mse; 50, 100 and 200 ㎍/mL) for 1 hrs, and then incubated with lipopolysaccharide (LPS; 500 ng/mL). Cell viability was measured by the MTT method, and nitric oxide (NO) was measured with griess reagent. In addition, pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). For anti-gastritis effect in vivo, acute gastritis was induced using 150 mM HCl/60% ethanol used ICR mice. WRT-mse (133 mg/kg) was pre treated for 3 days and then treated with 150 mM HCl/60% ethanol 1 hrs later. Then gastritis was observed and inflammatory cytokines in the gastric tissue was measured. Results : The 8 marker components of the WRT-mse were determined by simultaneous analysis using HPLC. WRT-mse was not toxic and inhibited pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α at NO production, protein and mRNA levels. Also, it was confirmed that WRT-mse improved bleeding and edema in gastritis, and suppresses inflammatory cytokines. Conclusion : In summary, our results suggest that the treatment of the WRT-mse reduced and improved the 150 mM HCl/60% ethanol induced acute gastritis and the inflammation caused by LPS stimulation in RAW 264.7 cells. Therefore, this study may provide useful drug or clinical evidence for WRT-mse to prevent inflammation.

Arthrospira (Spirulina) platensis Attenuates Dextran Sulfate Sodium-induced Colitis in Mice by Suppressing Key Pro-inflammatory Cytokines

( Francisca Adilfa De Oliveira Garcia ),( Helioswilton Sales-campos ),( Violet G. Yuen ),( Juliana Reis Machado ),( Glauce Socorro De Barros Viana ),( Carlo José Freire Oliveira ),( John H. Mcneill ) 대한소화기학회 2020 대한소화기학회지 Vol.76 No.3

Background/Aims: Therapies aimed at modulating cytokines have been used to treat inflammatory illnesses, such as inflammatory bowel disease. On the other hand, patients may become intolerant, refractory, or present with several side effects. Arthrospira (Spirulina) platensis (SPI) is a blue-green microalga with bioactive molecules that have been evaluated to treat inflammatory diseases. On the other hand, few studies have examined their effects on the production of specific cytokines and the intestinal architecture in dextran sulfate sodium (DSS)-induced colitis. Therefore, this study examined the effects of a treatment using SPI in a murine model of intestinal inflammation. Methods: All mice (C57BL/6 male) were evaluated daily for their food and water intake, bodyweight variations, and clinical signs of disease. Colon inflammation was induced by exposure to DSS for 6 consecutive days. SPI was given orally at 50, 100, and 250 mg/kg/day. ELISA was performed to assess the production of cytokines. Myeloperoxidase and nitric oxide were also investigated. The level of microscopic damage was assessed by staining colon sections with hematoxylin and eosin. Results: SPI attenuated the DSS-induced inflammation, with improvements in the clinical signs and a decrease in the production of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ. In addition, particularly at 250 mg/kg, SPI attenuated the severity of colitis by modulating the level of mucosal and submucosal cell infiltration, which preserved the epithelial barrier. Conclusions: SPI may be an alternative source of bioactive molecules with immunomodulatory properties, and has great potential to be used in the treatment of inflammatory diseases. (Korean J Gastroenterol 2020;76:150-158)