• Title, Summary, Keyword: Cytokines

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Cytokines and Depression (사이토카인과 우울증)

  • Kim, Yong-Ku
    • Korean Journal of Biological Psychiatry
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    • v.15 no.3
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    • pp.175-185
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    • 2008
  • Accumulating evidence has suggested the existence of reciprocal communication between immune, endocrine, and neurotransmitter system. Cytokine hypothesis of depression implies that increased pro-inflammatory cytokine such as -1, IL-6, IL-12, TNF-${\alpha}$, and IFN-${\gamma}$ in major depression, acting neuromodulators, play a key role in the mediation of behavioral, neuroendocrine, and neurochemical disturbances in depression. Concerning the relation between cytokines and serotonin metabolism, pro-inflammatory cytokines have profound effects on the metabolism of brain serotonin through the enzyme indoleamine-2,3-dioxygenase(IDO) that metabolizes tryptophan, the precursor of 5-HT to neurodegenerative quinolinate and neuroprotective kynurenate. The neurodegeneration process is reinforced by the neurotoxic effect of the hypercortisolemia during depression. From this perspective, it is possible that efficacy of antidepressants in the treatment of depression may, at least in part, rely on downregulation of pro-inflammatory cytokine synthesis. So, the use of cytokine synthesis inhibitors or cytokine antagonists may be a new treatment approach in depression. However, at present the question whether cytokines play a causal role in the onset of depression or are mere epiphenomena sustaining depressive symptoms remains to be elucidated. Nevertheless, cytokine hypothesis has created new perspectives in the study of psychological and pathophysiological mechanism that are associated with major depression, as well as the prospect for developing a new generation antidepressants.

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Discovery of Novel 4${\alpha}$ helix Cytokine by Hidden Markov Model Analysis

  • Du, Chunjuan;Zeng, Yanjun;Zhu, Yunping;He, Fuchu
    • Proceedings of the Korean Society for Bioinformatics Conference
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    • pp.41-44
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    • 2005
  • Cytokines play a crucial role in the immune and inflammatory responses. But because of the high evolutionary rate of these proteins, the similarity between different members of their family is very low, which makes the identification of novel members of cytokines very difficult. According to this point, a new bioinformatic strategy to identify novel cytokine of the short-chain and long-chain 4${\alpha}$ helix cytokine using hidden markov model (HMM) is proposed in the paper. As a result, two motifs were created on the two train data sets, which were used to search three different databases. In order to improve the result, a strict criterion is established to filter the novel cytokines in the subject proteins. Finally, according to their E-value, scores and the criterion, four subject proteins are predicted to be possible novel cytokines for each family respectively.

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Anti-inflammatory effect of chloroform fraction of Coptidis rhizoma on the production of inflammatory mediators from LPS-stimulated BV2 microglial cells (황련 클로로포름 분획물의 뇌신경소교세포로부터 염증매개물질 생성억제 효능 연구)

  • Park, Yong-Ki;Lee, Kyuong-Yeol
    • The Korea Journal of Herbology
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    • v.22 no.4
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    • pp.109-116
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    • 2007
  • Objectives : In the present study, we investigated anti-inflammatory effects of chloroform fraction of Coptidis rhizoma (CR-C) on the production of inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokines, tumor necrosis factor-alpha (TNF-${\alpha}$) and interleukin-1beta (IL-1${\beta}$) in LPS-stimulated BV2 microglial cells. Methods : Copriditis rhizoma was extracted with 80% methanol, and then extracted with chloroform. BV2 cells were pre-treated with CR-C, and stimulated with LPS. The cytotoxicity was determined by MTT assay. The production of NO and cytokines was measured by Griess assay and ELISA. The mRNA expression of inducible nirtic oxide synthase (iNOS) and cytokines were determined by RT-PCR. Results : CR-C significantly inhibited the production of NO. TNF-${\alpha}$ and IL-1${\beta}$ in a dose-dependent manner in LPS-stimulated BV2 cells. In addition, CR-C suppressed the mRNA expressions of iNOS and inflammatory cytokines induced by LPS stimulation. These results indicate that CR-C was involved in anti-inflammatory effects in activated microglia. Conclusion : The present study suggests that chloroform extract of Coptidis rhizoma can be useful as a potential anti-inflammatory agent for treatment of various neurodegenerative diseases.

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Pycnogenol Supplementation Retards Immune Dysfunction in Murine AIDS (MAIDS) After LP-BM5 Leukemia Virus Infection by Modulating Cytokine Secretion

  • Lee, Jeong-Min;Park, Kun-Young;Hwang, Kwon-Tack;Watson, Ronald R.
    • Preventive Nutrition and Food Science
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    • v.10 no.2
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    • pp.161-166
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    • 2005
  • We investigated the effect of pycnogenol (PYC) supplementation on retarding the immune dysfunction of CS7BL/6 mice after murine AIDS (MAIDS) development. Dysfunction of T and B cell mitogenesis from primary cultured splenocytes has been observed with retrovirus infection and PYC supplementation partially recovered the dysfunction of T and B cells. There was an abnormal shift of cytokine pattern with retrovirns infection, which was designated by the decreased secretion of Th1 cytokines and increased secretion of Th2 cytokines. PYC supplementation increased IL-2 and $IFN-\gamma$ secretion and decreased IL-4, IL-6, and $TNF-\alpha$ secretion, but it was not sufficient enough to maintain the normal level of these cytokines. Hepatic vitamin E level was significantly decreased by retrovirns infection, in accordance with increased hepatic lipid peroxidation level, whereas PYC supplementation normalized the hepatic level of vitamin E and lipid peroxidation. This study suggests that PYC supplementation may partially help retard the incidence of symptoms during MAIDS.

Th1/Th2 Cytokine Modulation in Human PBMC by Acanthopanax divaricatus var. albeofructus

  • Lyu, Su-Yun;Park, Won-Bong
    • Food Science and Biotechnology
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    • v.17 no.3
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    • pp.631-636
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    • 2008
  • Acanthopanax divaricatus var. albeofructus (ADA) have been shown to have various levels of activity such as antioxidant, anticancer, antivirus, and immunostimulatory effects. However, little is known about its mechanism related to the modulation of immune activities. In this study, a water extract of ADA leaves were used to treat human peripheral blood mononuclear cells (hPBMC) to determine the underlying mechanisms for the immunostimulatory effects. To characterize its immunomodulatory activity, the secretion level of various cytokines including IL-2, IL-4, IL-6, IL-10, IL-12, IFN-$\gamma$, and TNF-$\alpha$ were measured using enzyme-linked immunosorbent assay (ELISA). Treatment of hPBMC with ADA leaf extract in an in vitro experiment induced various Th1 cytokines in a dose-dependent manner. A significant increase of IL-2, IL-12, IFN-$\gamma$, and TNF-$\alpha$ secretion was observed in the presence of ADA leaf extract. In contrast, Th2 cytokines including IL-4 and IL-6 were suppressed. There was no significant change in IL-10 release. Our results showed an increase in Th1 and a decrease in Th2 cytokine secretion which suggests that ADA may influence the immune response towards a predominance of Th1 cytokines in the immune system.

Cordyceps militaris Enhances MHC-restricted Antigen Presentation via the Induced Expression of MHC Molecules and Production of Cytokines

  • Shin, Seulmee;Park, Yoonhee;Kim, Seulah;Oh, Hee-Eun;Ko, Young-Wook;Han, Shinha;Lee, Seungjeong;Lee, Chong-Kil;Cho, Kyunghae;Kim, Kyungjae
    • IMMUNE NETWORK
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    • v.10 no.4
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    • pp.135-143
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    • 2010
  • Background: Cordyceps militarys water extract (CME) has been reported to exert antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of CME on the antigen presenting function of antigen presenting cells (APCs). Methods: Dendritic cells (DCs) were cultured in the presence of CME, and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing the efficacy of OVA, peptide presentation by DCs were evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through western blot analysis. Results: CME enhanced both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the expression of both MHC class I and II molecules was enhanced, but there was no changes in the phagocytic activity of exogenous OVA. Furthermore, CME induced the protein levels of iNOS, COX-2, proinflammatory cytokines, and nuclear p65 in a concentration-dependent manner, as determined by western blot. Conclusion: These results provide an understanding of the mechanism of the immuno-enhancing activity of CME on the induction of MHC-restricted antigen presentation in relation to their actions on APCs.

Effect of Baicalin on the Ex vivo Production of Cytokines in Pristane-Induced Lupus Mice (프리스탄 유도한 루푸스 생쥐에서 사이토카인 Ex vivo 생산에 미치는 Baicalin의 효과)

  • Chae, Byeong Suk
    • YAKHAK HOEJI
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    • v.60 no.1
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    • pp.21-28
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    • 2016
  • Systemic lupus erythematosus (SLE) is characterized by dysregulatory production of proinflammatory cytokines and helper T (Th) cytokine-dependent autoantibody production. This study aims to investigate the protective effect of baicalin on the dysregulatory production of proinflammatory cytokines and Th cytokines in pristane-induced lupus mice. Mice were received i.p. a single injection of 0.5 ml of pristane, and then, later about 3 months, were used as a pristane-induced lupus model. The pristane-induced lupus mice were administrated orally with baicalin 50 mg/kg once in a day for 10 days. Immune cells obtained from the pristane-primed lupus control group (lupus control) and baicalin-treated pristaneprimed lupus mouse group (BAC lupus) were cultured for 24 h or 36 h with/without mitogens. These results demonstrated that LPS-induced production of macrophage and splenic TNF-${\alpha}$ and Con A-induced production of thymic IFN-${\gamma}$ were attenuated in BAC lupus compared to lupus control, while LPS-stimulated production of macrophage IL-10, Con A-stimulated production of splenic IL-10 and, $PGE_2$-reduced production of splenic IFN-${\gamma}$ enhanced. Therefore, these findings suggest that baicalin may protect from autoimmunity and disease activity in lupus via modulatory effect of proinflammatory cytokine overproduction and Th cytokine imbalance.

The combination of canagliflozin and omega-3 fatty acid ameliorates insulin resistance and cardiac biomarkers via modulation of inflammatory cytokines in type 2 diabetic rats

  • Safhi, Mohammed Mohsen;Anwer, Tarique;Khan, Gyas;Siddiqui, Rahimullah;Sivakumar, Sivagurunathan Moni;Alam, Mohammad Firoz
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.5
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    • pp.493-501
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    • 2018
  • The present study was carried out with the hypothesis that combination of canagliflozin and omega-3 fatty acid may have potential effect on insulin level, insulin resistance, cardiac biomarkers, inflammatory cytokines and histological studies in type 2 diabetes mellitus (DM). Type 2 DM was induced by injecting nicotinamide (120 mg/kg, i.p.) 15 min before STZ (60 mg/kg) injection. Canagliflozin (5 and 10 mg/kg) and omega-3 fatty acid (300 mg/kg) were given for 28 days after confirmation of diabetes. Biochemical estimations revealed elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines in diabetic group. Daily dosing of alone canagliflozin and omega-3 fatty acid slightly reduced elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines ($IL-1{\beta}$, IL-2, and $TNF{\alpha}$), whereas canagliflozin and omega-3 fatty acid combination has reduced these biochemical parameters significantly when compared with diabetic group. Similarly in diabetic group the levels of cardiac biomarkers such as lipid profile, LDH, CKMB and troponin were significantly increased. Elevated levels of cardiac biomarkers were significantly reduced after daily dosing of alone canagliflozin and omega-3 fatty acid. Canagliflozin and omega-3 fatty acid combination has offered better improvement in cardiac biomarkers compared to alone canagliflozin and omega-3 fatty acid. Histopathological analysis also supported the above hypothesis that combination therapy (canagliflozin and omega-3 fatty acid) offered better protection against degenerative changes in ${\beta}-cells$ of pancreas as compared to alone treatment with these drugs. Thus the present study revealed that canagliflozin and omega-3 fatty acid can be used as potential combination therapy in type 2 DM along with cardiac complication.

Lysophosphatidic acid enhances breast cancer cells-mediated osteoclastogenesis

  • Nam, Ju-Suk;Sharma, Ashish Ranjan;Nguyen, Lich Thi;Jagga, Supriya;Lee, Yeon-Hee;Sharma, Garima;Lee, Sang-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.5
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    • pp.503-511
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    • 2018
  • Lysophosphatidic acid (LPA) is known to play a critical role in breast cancer metastasis to bone. In this study, we tried to investigate any role of LPA in the regulation of osteoclastogenic cytokines from breast cancer cells and the possibility of these secretory factors in affecting osteoclastogenesis. Effect of secreted cytokines on osteoclastogenesis was analyzed by treating conditioned media from LPA-stimulated breast cancer cells to differentiating osteoclasts. Result demonstrated that IL-8 and IL-11 expression were upregulated in LPA-treated MDA-MB-231 cells. IL-8 was induced in both MDA-MB-231 and MDA-MB-468, however, IL-11 was induced only in MDA-MB-231, suggesting differential LPARs participation in the expression of these cytokines. Expression of IL-8 but not IL-11 was suppressed by inhibitors of PI3K, NF-kB, ROCK and PKC pathways. In the case of PKC activation, it was observed that $PKC{\delta}$ and $PKC{\mu}$ might regulate LPA-induced expression of IL-11 and IL-8, respectively, by using specific PKC subtype inhibitors. Finally, conditioned Medium from LPA-stimulated breast cancer cells induced osteoclastogenesis. In conclusion, LPA induced the expression of osteolytic cytokines (IL-8 and IL-11) in breast cancer cells by involving different LPA receptors. Enhanced expression of IL-8 by LPA may be via ROCK, PKCu, PI3K, and NFkB signaling pathways, while enhanced expression of IL-11 might involve $PKC{\delta}$ signaling pathway. LPA has the ability to enhance breast cancer cells-mediated osteoclastogenesis by inducing the secretion of cytokines such as IL-8 and IL-11.

The Effect of Artemisia Capillaris Herba on Ethanol-Induced Cytokines(TNF-${\alpha},IL-1{\alpha}$) Secretion in Hep G2 Cells (인진호가 Hep G2 세포에서 에탄올 매개성 Cytokine 분비에 미치는 영향)

  • Sim, Jung-Sub;Kim, Il-Hwan;Kim, Gang-San;Kagn, Byung-Ki;Choi, Su-Deock
    • The Journal of Internal Korean Medicine
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    • v.22 no.1
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    • pp.87-93
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    • 2001
  • A human hepatoma cell line, Hep G2 cells, is reliable for the study of alcohol-induced hepatotoxicity. The aim of this study is to determine the relationship between TNF-${\alpha}$, IL-$1{\alpha}$ production and EtOH-induced cytotoxicity on Hep G2 cells. The cells were incubated with EtOH in the presence of Artemisia Capillaris Herba(AC) for 24 hours and in the absence of AC for 48 hours. Cytoviability and cytokines release were analyzed by MTT assay and enzyme linked immunosorbent assay (ELISA), respectively. After 24 hours of EtOH exposure, the cytoviability had markedly decreased, and the release of cytokines had increased. The increased amount of cytokines contributed to EtOH-induced cytotoxicity. Anti-TNF-${\alpha}$ and IL-$1{\alpha}$ antibodies almost abolished it. Interestingly, EtOH-induced cytotoxicity and cytokines production were inhibited by AC. Moreover, when AC was used in combination with antibodies, there was a marked inhibition of EtOH-induced cytotoxicity. These results suggest that EtOH-induced cytotoxicity may regulate, by various factors, and AC may prevent the cytotoxicity through partial inhibition of the $TNF-{\alpha}$ and IL-$1{\alpha}$ secretion.

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