• Title/Summary/Keyword: blood cytokine

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Antioxidant and anti-inflammatory activities of water extracts and ethanol extracts from Portulaca oleracea L. (쇠비름 물, 에탄올 추출물의 항산화 및 항염증 활성)

  • Kim, Dong-Gyu;Shin, Jung-Hye;Kang, Min-Jung
    • Food Science and Preservation
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    • v.25 no.1
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    • pp.98-106
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    • 2018
  • Portulaca oleracea L., a species of Portulacaceae, is ubiquitous. It is a well-known traditional Chinese medicine for removing heat, counteracting toxicity, cooling blood, and maintaining hemostasia; it is also used as antidysentery agent. This study investigated the anti-oxidative and anti-inflammatory activities of water and ethanol extracts from P. oleracea. The total polyphenol content ($21.08{\pm}0.03mg\;GAE/g$) and total flavonoid content ($5.45{\pm}0.76mg\;QE/g$) of the ethanolic extracts were higher than those of the water extracts. The antioxidative activities were determined by evaluating the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging activity and by the ferric reducing antioxidant potential (FRAP) assay. The ABTS radical scavenging activity of the water extract (75.53%) was higher in those of the water extract (67.03%) at concentration of $1,000{\mu}g/mL$. The DPPH radical scavenging activity and FRAP of the ethanol extract were higher than those of the water extract. We also investigated the anti-inflammatory activity of the P. oleracea extracts in LPS-stimulated Raw 264.7 cells. The production levels of nitric oxide (NO) and reactive oxygen species (ROS) significantly decreased with an increasing concentration of the extract. The expression levels of pro-inflammatory cytokines (tumor necrosis faction (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6) were significantly lower in the ethanol extract than in the LPS alone treatment group. Based on these results, ethanolic extract from P. oleracea could be an effective antioxidant and anti-inflammatory agent.

Broiler responses to dietary 3,4,5-trihydroxybenzoic acid and oregano extracts under Eimeria challenge conditions

  • Yu, Myunghwan;Jeon, Jong Oh;Cho, Hyun Min;Hong, Jun Seon;Kim, Yu Bin;Nawarathne, Shan Randima;Wickramasuriya, Samiru Sudharaka;Yi, Young-Joo;Lee, Hans;Wan, Vannie;Ng, Noele Kai Jing;Tan, Chuan Hao;Heo, Jung Min
    • Journal of Animal Science and Technology
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    • v.63 no.6
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    • pp.1362-1375
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    • 2021
  • This study was conducted to evaluate the efficacy of a combination 3,4,5-trihydroxybenzoic acid (THB) and oregano extracts (i.e., Carvacrol and Thymol) at intake/dietary different levels on growth performance, intestinal health indicators, immune responses and fecal oocyst shedding in broiler chickens under Eimeria challenged condition. A total of 336 one-day-old broilers were randomly assigned to one of six dietary treatments with seven replications per treatment. Dietary treatments were: i) Non-challenged bird without any dietary treatment (NCNT), ii) Challenged bird without any dietary treatment (CNT), iii) Challenged birds fed a THB diet (0.1 g/kg, THB), iv) Challenged birds fed a combination of THB and oregano extracts diet (0.1 g/kg, COM 100), and a gradual increase of combination of THB and oregano extracts likely v) 0.15 g/kg (COM 150), and 0.2 g/kg (COM 200). On day 14, all groups except for NCNT have orally challenged with a 10-fold dose of Livacox® T anticoccidial vaccine to trigger coccidiosis. The results indicated that Eimeria-challenged broilers fed COM 100 and COM 200 diets increased (p < 0.05) body weight than CNT diet on day 35. Furthermore, birds fed COM 100 and COM 200 diets increased (p < 0.05) average daily gain compared to those fed CNT diets for the entire experimental period. There is no significant (p > 0.05) in average daily feed intake, feed efficiency between NCNT and birds fed with combined THB and oregano extracts for the entire experimental period. A combination of THB and oregano extract regardless of concentration levels or THB alone reduced (p < 0.05) lesion score in ileum compared to the CNT diet for 7 days post-infection (dpi). Birds fed COM 100 diet had lower (p < 0.05) intestinal lesion scores in jejunum and caeca on 7 dpi compared to those were in the CNT diet. No (p > 0.05) difference was observed in the oocysts per gram of feces count, intestinal morphology, carcass traits and blood cytokine concentration among the infected treatments. Collectively, we conclude that birds fed with a combination of THB and oregano extracts regardless of the ratios that were used demonstrated better recovery of health after the coccidial challenge than using only THB alone.

Anti-inflammatory effect of Euonymi Lignum Suberalatum in LPS-activated Raw 264.7 cells and CA-induced paw edema rat model (귀전우(鬼箭羽)의 in vitro 및 in vivo에서의 염증억제효과)

  • Jeon, Chang Kwon;Park, Sang Mi;Park, Chung A;Byun, Sung Hui;Kim, Sang Chan
    • Herbal Formula Science
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    • v.27 no.2
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    • pp.101-120
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    • 2019
  • PURPOSE : Euonymi Lignum Suberalatum (EL) is the stem fin of Euonymi alatus. In traditional Korean medicine, EL is used for treatment of uterine bleeding, metritis and static blood. Recently, many studies have reported several pharmacological effects of EL including anticancer, antimicrobial, antidiabetic activity, and anti-oxidative stress. However, the mechanisms underlying anti-inflammatory effects by the EL is not established. METHODS : To investigate anti-inflammatory effects of Euonymi Lignum Suberalatum Water (ELWE), Raw 264.7 cells were pre-treated with $10-300{\mu}g/mL$ of ELWE, and then exposed to $1{\mu}g/mL$ of LPS. Levels of NO, IL-6, $IL-1{\beta}$ and $TNF-{\alpha}$ were detected by ELISA kit. Expression of pro-inflammatory proteins were determined by immunoblot analysis. To evaluate the anti-inflammatory effect in vivo, rat paw edema volume, and expressions of COX-2 and iNOS proteins in carrageenan (CA)-induced rat paw edema model. RESULTS : NO production activated by LPS, was decreased by $30-300{\mu}g/mL$ of ELWE. Production of inflammatory mediators such as $TNF-{\alpha}$, ILs, $PGE_2$ were decreased by ELWE 100 and $300{\mu}g/mL$. In addition, ELWE reduced LPS-mediated iNOS and COX-2 expression. Moreover, ELWE increased $I-{\kappa}B{\alpha}$ expression in cytoplasm and decreased $NF-{\kappa}B$ expression in nucleus. In vivo study, ELWE reduced the increases of paw swelling, and expression of iNOS and COX-2 proteins in paw edema induced by CA injection. CONCLUSION : The results indicate that ELWE could inhibit the acute inflammatory response, via modulation of $NF-{\kappa}B$ activation. Furthermore, inhibition of rat paw edema induced by CA is considered as clear evidence that ELWE may be a useful source to treat acute inflammation.

Comparison of Overall Immunity Levels among Workers at Grape Orchard, Rose Greenhouse, and Open-Field Onion Farm

  • Maharjan, Anju;Gautam, Ravi;Jo, JiHun;Acharya, Manju;Lee, DaEun;Pramod, Bahadur KC;Gim, Jin;Sin, Sojung;Kim, Hyocher;Kim, ChangYul;Lee, SooYeon;Lee, SooJin;Heo, Yong;Kim, HyoungAh
    • Safety and Health at Work
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    • v.13 no.2
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    • pp.248-254
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    • 2022
  • Background: Occupational hazards in crop farms vary diversely based on different field operations as soil management, harvesting processes, pesticide, or fertilizer application. We aimed at evaluating the immunological status of crop farmers, as limited systematic investigations on immune alteration involved with crop farming have been reported yet. Methods: Immunological parameters including plasma immunoglobulin level, major peripheral immune cells distribution, and level of cytokine production from activated T cell were conducted. Nineteen grape orchard, 48 onion open-field, and 21 rose greenhouse farmers were participated. Results: Significantly low proportion of natural killer (NK) cell, a core cell for innate immunity, was revealed in the grape farmers (19.8±3.3%) in comparison to the onion farmers (26.4±3.1%) and the rose farmers (26.9±2.5%), whereas cytotoxic T lymphocyte proportion was lower in the grape and the onion farmers than the rose farmers. The proportion of NKT cell, an immune cell implicated with allergic response, was significantly higher in the grape (2.3±0.3%) and the onion (1.6±0.8%) farmers compared with the rose farmers (1.0±0.4%). A significantly decreased interferon-gamma:interleukin-13 ratio was observed from ex vivo stimulated peripheral blood mononuclear cells of grape farmers compared with the other two groups. The grape farmers revealed the lowest levels of plasma IgG1 and IgG4, and their plasma IgE level was not significantly different from that of the onion or the rose farmers. Conclusion: Our finding suggests the high vulnerability of workplace-mediated allergic immunity in grape orchard farmers followed by open-field onion farmers and then the rose greenhouse farmers.

Inflammatory cytokines in patients with pesticide poisoning: a pilot study (농약 중독에 의한 혈중 염증성 사이토카인의 영향에 대한 예비 연구)

  • Kim, Hyun Joon;Kim, Wook-Joon;Lee, Dong Wook;Jung, Seung-Hyun;Cho, Nam-Jun;Park, Samel;Lee, Eun Young;Gil, Hyo-Wook
    • Journal of The Korean Society of Clinical Toxicology
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    • v.20 no.1
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    • pp.15-21
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    • 2022
  • Purpose: Acute pesticide poisoning is lethal and can lead to death. A few studies about the effects of acute pesticide poisoning have focused on the immune system. In the current study, we preliminarily investigated the changes in blood inflammatory cytokine levels in acute pesticide poisoning patients. Methods: In this study, we prospectively investigated the inflammatory cytokines in patients with acute pesticide poisoning. This study included patients admitted from February 2021 to November 2021 with a diagnosis of intentional poisoning by pesticide ingestion. The inflammatory cytokines measured were IFN-γ, IL-1β, IL-6, and TNF-α. Results: Totally, 27 patients were enrolled in this study. The types of pesticide ingested were glufosinate (n=6), glyphosate (n=8), organophosphate (n=4), pyrethroid (n=2), and others (n=7). The levels of inflammatory cytokines obtained were as follows: IFN-γ 2.78±8.03 pg/ml, IL-1β 2.62±2.03 pg/ml, IL-6 44.58±80.16 pg/ml, and TNF-α 11.80±15.60 pg/ml. The overall mortality rate was 11.1% (3/27), and levels of IL-1β and TNF-α were significantly higher in the death group compared to the survival group. Conclusion: Increased levels of IL-6 and TNF-α were observed in patients with acute pesticide poisoning. IL-1β and TNF-α were significantly higher in the death group as compared to the survival group. Our results indicate the occurrence of an inflammatory response due to the activation of immune cells by pesticide poisoning. Future large-scale studies need to be conducted to investigate the application of inflammatory cytokines as predictors and therapeutic targets.

Anti-fatigue effect of tormentic acid through alleviating oxidative stress and energy metabolism-modulating property in C2C12 cells and animal models

  • Ho-Geun Kang;Jin-Ho Lim;Hee-Yun Kim;Hyunyong Kim;Hyung-Min Kim;Hyun-Ja Jeong
    • Nutrition Research and Practice
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    • v.17 no.4
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    • pp.670-681
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    • 2023
  • BACKGROUND/OBJECTIVES: Oxidative stress is caused by reactive oxygen species and free radicals that accelerate inflammatory responses and exacerbate fatigue. Tormentic acid (TA) has antioxidant and anti-inflammatory properties. Thus, the aim of present study is to determine the fatigue-regulatory effects of TA in H2O2-stimulated myoblast cell line, C2C12 cells and treadmill stress test (TST) and forced swimming test (FST) animal models. MATERIALS/METHODS: In the in vitro study, C2C12 cells were pretreated with TA before stimulation with H2O2. Then, malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase (CK) activity, tumor necrosis factor (TNF)-α, interleukin (IL)-6, superoxide dismutase (SOD), catalase (CAT), glycogen, and cell viability were analyzed. In the in vivo study, the ICR male mice were administered TA or distilled water orally daily for 28 days. FST and TST were then performed on the last day. In addition, biochemical analysis of the serum, muscle, and liver was performed. RESULTS: TA dose-dependently alleviated the levels of MDA, LDH, CK activity, TNF-α, and IL-6 in H2O2-stimulated C2C12 cells without affecting the cytotoxicity. TA increased the SOD and CAT activities and the glycogen levels in H2O2-stimulated C2C12 cells. In TST and FST animal models, TA decreased the FST immobility time significantly while increasing the TST exhaustion time without weight fluctuations. The in vivo studies showed that the levels of SOD, CAT, citrate synthase, glycogen, and free fatty acid were increased by TA administration, whereas TA significantly reduced the levels of glucose, MDA, LDH, lactate, CK, inflammatory cytokines, alanine transaminase, aspartate transaminase, blood urea nitrogen, and cortisol compared to the control group. CONCLUSIONS: TA improves fatigue by modulating oxidative stress and energy metabolism in C2C12 cells and animal models. Therefore, we suggest that TA can be a powerful substance in healthy functional foods and therapeutics to improve fatigue.

The Effect of CV12, ST25, ST36 Acupuncture in General Diet and High Fat Diet Rat (고지방식이 및 일반식이 백서에 대한 중완·천추·족삼리 침자의 유효성 검증)

  • Kyeong-Soo Kim;Myeong-Hun Kim;Jae-Uk Sul;Eun-Ju Kim;Hong-Seok Son;Chang-Su Na
    • Korean Journal of Acupuncture
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    • v.40 no.3
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    • pp.109-127
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    • 2023
  • Objectives : It was conducted to experimentally analyze the effects of acupuncture treatment at CV12, ST25, and ST36 on weight, FBCS, fat metabolism, microbiome, and metabolome changes in the general diet rat and the high-fat diet rat. Methods : It was classified into four groups: general diet & non-treatment group (ND), general diet & acupuncture treatment group (ND+AT), high-fat diet & non-treatment group (HFD), and high-fat diet & acupuncture treatment group (HFD-AT). After acupuncture treatment was performed on CV12, ST25, and ST36, changes in body weight, FBCS, fat metabolism, microbiome, and metabolome were analyzed. Results : Compared to the ND group, acupuncture treatment performed on CV12, ST25, and ST36 in the ND+AT group had no significant effect. Compared to the HFD group, CV12, ST25, and ST36 acupuncture in the HFD+AT group reduced weight, fat weight, inflammatory cytokine IL-6 expression, and lipid droplet accumulation in liver tissue. Acupuncture can promote fat metabolism and relieve inflammatory conditions. Differences in diversity between ND and HFD groups were clear in changes in microbiome, fecal metabolites, and serum metabolites. As a result of some microbiome and metabolites involved in fat decomposition, intestinal lipid absorption, and blood lipid concentration control, such as Intestinimonas, Ruminococcus 1, pyroglutamic acid, tryptophan, and inositol, it was observed that the acupuncture treatment effect was evident in the disease-induced imbalance. Conclusions : Acupuncture treatment performed on CV12, ST25, ST36 clearly observed various regulatory actions on obesity induced by high-fat diet, confirming that the action of acupuncture treatment mainly plays a role in controlling an unbalanced state.

Thymus quinquecostatus Extracts Suppress IFN-γ/TNF-α -induced Inflammatory Cytokine in Lung Fibroblast MRC-5 Cells

  • Young-Jae Song;Sa-Haeng Kang;Jae-Bin Seo;Se-Woong Ko;Ju-Ryoun Soh;Jeong-Hyang Park;Dong-Keun Kim;Tae-Hyun Kim;Hyuck-Se Kwon;Na Young Lee;Jong-Sik Jin
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2020.12a
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    • pp.81-81
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    • 2020
  • Pneumonia is infection of air sacs in lungs by bacteria, viruses, fungi and abnormal atmosphere condition. That causes to inflammation and fills up with pus and fulid in air sacs. The symptoms of pneumonia are heavy cough, fever, shortness and rapid respiration and sputum with blood. Also, that remains sequela after the recovery. Thymus quinquecostatus (TQ) has a strong antibacterial effect. That has been used a natural medicine for bronchitis, asthma and nervous inflammation. In this study evaluated anti-inflammatory effects of TQ on IFN (interferon)-γ/TNF (tumor necrosis factor)-α (20 ng/ml) stimulation. MRC-5 cells were seeded at 1 × 105 cells/well in a 24-well plate and stabilized overnight at 37℃. The cells were treated with various concentrations of TQ extracts (DW, 30, 50, 70, 95% EtOH, 0.1~100 mg/ml) for 4h, Subsequently IFN-γ/TNF-α (20 ng/ml) was added to each well and incubated over 12h. the production of inflammatory cytokines were measured by Enzyme-linked immunosorbentassay(ELISA) method. The absorbance was measured at 450 nm using microplate reader. The treatment with TQ extract at dose of 0.1 to 100 mg/ml did not show cytotoxicity in MRC-5 cells (showed cytotoxicity at 95% EtOH 100 mg/ml). The results demonstrated that stimulation of TNF-α/IFN-γ significantly increased the production of inflammatory mediators in the MRC-5 cells compared with unstimulated cells. By contrast, treatment with TQ extreats doses of 0.001 to 10 mM significantly suppressed the production of IL-6 and IL-8. Especially. The higher percent of ethyl alcohol extracts suppressed the production of inflammatory cytokines. This results are considered that essential oil of TQ is extracted according to ethyl alcohol percent. Therefore, TQ has potential to mitigate pulmonary disease that can be used a medicine for pneumonia

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Compilation of 104 Experimental Theses on the Antitumor and Immuno-activating therapies of Oriental Medicine (한의학의 항종양 면역치료에 관한 연구 -1990년 이후 발표된 실험논문을 중심으로-)

  • Kang Yeon Yee;Kim Tai Im;Park Jong Ho;Kim Sung Hoon;Park Jong Dai;Kim Dong Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.1-24
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    • 2003
  • This study was done to compile 104 experimental theses which are related to the antitumor and immuno-activating therapies between February 1990 through February 2002. Master's and doctoral theses were dassified by schools, degrees, materials, effects, experimental methods of antitumor and immunoactivity, and results. The following results were obtained from this study : 1. Classifying the theses by the school, 34.6% were presented by Daejeon University, 29.8% by Kyung-hee University and 11.5% by Won-kwang University. Of all theses, 51.0% were aimed for the doctoral degree and 43.3% were for the master's degree. All of three universities have their own cancer centers. 2. Classifying the theses by herb materials, complex prescription accounted for 60.3%, single herb accounted for 24.8% and herbal acupuncture accounted for 14.2%. Considering the key principles of the traditional medicine, complex prescription was much more thoroughly studied than single herb prescription. The results showed that the complex prescription had both antitumor activity and immuno-activating activity, which might reflects on multi-activation mechanisms by complex components. 3. Classifying the theses by the efficacy of herbs examined, in single herb, invigorating spleen and supplementing was 35.5%, expelling toxin and cooling was 29.0%, activating blood flow and removing blood stasis was 12.9%. In herbal acupuncture, invigorating spleen and supplementing was 52.9%, expelling toxin and cooling was 29.4%. In complex prescription, pathogen-free status was 41.9%, strengthening healthy qi to eliminate pathogen was 35.5%, strengthening healthy qi was 22.6%. It is presumed that the antitumor and immunoactivating therapy based on syndrome differentiation is the best way to develop oriental oncology. 4. Classifying the theses by antitumor experiments, cytotoxic effect was 48.1 %, survival time was 48.1 % and change of tumor size was 42.3%. Survival rate was not necessarily correlated with cytotoxicity. These data reflect the characteristic, wholistic nature of the oriental medicine which is based on BRM (biological response modifier). 5. Classifying the theses by immunoactivating experiments, hemolysin titer was 51.0%, hemagglutinin titer was 46.2% and NK cell's activity was 44.2%. In the future studies, an effort to elucidate specific molecular and cellular mechanisms of cytokine production in the body would be crucial. 6. Classifying the theses according to the data in terms of antitumor activity, 50% was evaluated good, 24.0% was excellent, and 15.5% have no effect. In an evaluation of immuno-activating activity, 35.9% was excellent and 18.0% showed a little effect. The index point, as described here, may helps to use experimental data for clinical trials. Changes in index points by varying dosage implicate the importance of oriental medical theory for prescription. 7. In 167 materials, IIP (immunoactivating index point, mean : 3.12±0.07) was significantly higher than AIP(antitumor index point, mean : 2.83±0.07). These data demonstrate that the effect of herb medicine on tumor activity depends more on immunoactivating activity than antitumor activity. This further implies that the development of herbal antitumor drugs must be preceded by the mechanistic understanding of immunoactivating effect. 8. After medline-searching tumor and herb-related articles from NCBI web site, we conclude that most of the studies are primarily focused on biomolecular mechanisms and/or pathways. Henceforth, we need to define the biomolecular mechanisms and/or pathways affected by herbs or complicated prescriptions. 9. Therefore, the most important point of oriental medical oncology is to conned between experimental results and clinical trials. For the public application of herbal therapy to cancer, it is critical to present the data to mass media. 10. To develop the relationship of experimental results and clinical trials, university's cancer clinic must have a long-range plan related to the university laboratories and, at the same time, a regular consortium for this relationship is imperative. 11. After all these efforts, a new type herbal medicine for cancer therapy which is to take care of the long-term administering and safety problem must be developed. Then, it would be expected that anti-tumor herbal acupuncture can improve clinical symptoms and quality of life (QOL) for cancer patients. 12. Finally, oriental medical cancer center must be constructed in NCC (National Cancer Center) or government agency for the development of oriental medical oncology which has international competitive power.

Role of Immune Response to Type II Collagen in the Pathogenesis of Rheumatoid Arthritis (류마티스 관절염 병인에서 제2형 콜라겐에 대한 면역반응의 역할)

  • Jung, Young Ok;Hong, Seung-Jae;Kim, Ho-Youn
    • IMMUNE NETWORK
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    • v.3 no.1
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    • pp.1-7
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    • 2003
  • Type II collagen (CII), major component of hyaline cartilage, has been considered as an auto-antigen in rheumatoid arthritis (RA). However, the clinical and biological significances with regard to the CII autoimmunity need to be clarified in human RA. The presence of antibodies to CII has been identified in sera, synovial fluid, and cartilage of patients with RA. In our study, the increased titer of IgG anti-CII in sera was well correlated with C-reactive protein, suggesting that this antibody may reflect the inflammatory status of RA. The titer of anti-CII antibodies (anti-CII Abs) tended to be higher in early stages of diseases. In our extending study, among 997 patients with RA, 269 (27.0%) were positive for circulatory IgG antibody to CII, those levels were fluctuated over time. It is hard to assess the significant amount of T cell responses to CII and CII (255~274) in RA. By using a sensitive method of antigen specific mixed lymphocyte culture, we can detect the presence of CII-reactive T cells in peripheral blood mononuclear cells of RA patients. Sixty seven (46.9%) of 143 patients showed positive CII reactive T cell responses to CII or CII (255~274). The frequencies of CII reactive T cells were more prominent in inflamed synovial fluid (SF) than in peripheral blood. These T cells could be clonally expanded after consecutive stimulation of CII with feeding of autologous irradiated antigen presenting cells (APC). Moreover, the production of Th1-related cytokine, such as IFN-${\gamma}$, was strongly up-regulated by CII reactive T cells. These data suggest that T cells responding to CII, which are probably presenting the IFN-${\gamma}$ producing cells, may play an important role in the perpetuation of inflammatory process in RA. To evaluate the effector function of CII reactive T cells, we investigated the effect of CII reactive T cells and fibroblasts-like synoviocytes (FLS) interaction on the production of pro-inflammatory cytokines. When the CII reactive T cells were co-cultured with FLS, the production of IL-15 and TNF-${\alpha}$ from FLS were significantly increased (2 to 3 fold increase) and this increase was clearly presented in accord to the expansion of CII reactive T cells. In addition, the production of IFN-${\gamma}$ and IL-17, T cell derived cytokines, were also increased by the co-incubation of CII reactive T cells with FLS. We also examined the impact of CII reactive T cells on chemokines production. When FLS were co-cultured with CII stimulated T cells, the production of IL-8, MCP-1, and MIP-1${\alpha}$ were significantly enhanced. The increased production of these chemokines was strongly correlated with increase the frequency of CII reactive T cells. Conclusively, immune response to CII was frequently found in RA. Activated T cells in response to CII contributed to increase the production of proinflammatory cytokines and chemokines, which were critical for inflammatory responses in RA. The interaction of CII-reactive T cells with FLS further augmented this phenomenon. Taken together, our recent studies have suggested that autoimmunity to CII could play a crucial role not only in the initiation but amplification/perpetuation of inflammatory process in human RA.