• Title/Summary/Keyword: in vitro immunomodulation

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Anti-inflammatory and utero-relaxant effect of α-bisabolol on the pregnant human uterus

  • Munoz-Perez, Victor Manuel;Ortiz, Mario I.;Ponce-Monter, Hector A.;Monter-Perez, Vicente;Barragan-Ramirez, Guillermo
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.4
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    • pp.391-398
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    • 2018
  • The aim of this study was to evaluate the in vitro anti-inflammatory and utero-relaxant effect of ${\alpha}$-bisabolol on the pregnant human myometrium. Samples from the pregnant human myometrium were used in functional tests to evaluate the inhibitory effect of ${\alpha}$-bisabolol (560, 860, 1,200 and $1,860{\mu}M$) on spontaneous myometrial contractions. The intracellular cyclic adenosine monophosphate (cAMP) levels generated in response to ${\alpha}$-bisabolol in human myometrial homogenates were measured by ELISA. The anti-inflammatory effect of ${\alpha}$-bisabolol was determined through the measurement of two pro-inflammatory cytokines, tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$) and interleukin $(IL)-1{\beta}$, and the anti-inflammatory cytokine IL-10, in pregnant human myometrial explants stimulated with lipopolysaccharide (LPS). Forskolin was used as a positive control to evaluate the cAMP and cytokine levels. ${\alpha}$-Bisabolol was found to induce a significant inhibition of spontaneous myometrial contractions at the highest concentration level (p<0.05). ${\alpha}$-Bisabolol caused a concentration-dependent decrease in myometrial cAMP levels (p<0.05) and a concentration-dependent decrease in LPS-induced $TNF{\alpha}$ and $IL-1{\beta}$ production, while IL-10 production did not increase significantly (p>0.05). The anti-inflammatory and utero-relaxant effects induced by ${\alpha}$-bisabolol were not associated with an increase in cAMP levels in pregnant human myometrial samples. These properties place ${\alpha}$-bisabolol as a potentially safe and effective adjuvant agent in cases of preterm birth, an area of pharmacological treatment that requires urgent improvement.

In vitro effects of monophosphoryl lipid A and Poly I:C combination on equine cells

  • Dong-Ha Lee;Eun-bee Lee;Jong-pil Seo ;Eun-Ju Ko
    • Journal of Veterinary Science
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    • v.24 no.3
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    • pp.37.1-37.14
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    • 2023
  • Background: Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans. Objectives: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs). Methods: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination. The mRNA expression of interferon gamma (IFN-γ), interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-12p40, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) was determined using real-time polymerase chain reaction. Results: The combination of MPL and Poly I:C significantly upregulated immunomodulatory responses in equine cells/ without cytotoxicity. The combination induced greater mRNA expression of pro-inflammatory cytokines IFN-γ and IL-6 than MPL or Poly I:C stimulation alone in PBMCs. In addition, the combination induced significantly higher mRNA expression of IL-1β, IL-6, and IL-12p40 in MoDCs, and IL-8, MCP-1, and VEGF in BM-MSCs compared to stimulation with a single TLR agonist. Conclusions: The combination of MPL and Poly I:C can be used as a potential adjuvant candidate for vaccines to aid in preventing infectious diseases in horses.

The Effect of Sopungchungyoung-tang on Activity of CD4 T cell

  • Choi Young Jin;Kang Hee;Myung Eu Gene;Shim Bum Sang;Choi Seung Hoon;Kim Sung Hun;Ahn Kyoo Seok
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.2
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    • pp.599-605
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    • 2004
  • Sopungchungyoung-tang (SCT) has been widely used in Korea as a treatment of atopic dermatitis. SCT consists of Talcum, Rehmannia glutinosa, Angelica sinensis, Paeonia lactiflora, Cnidium officinale, Ledebouriella divaricata, Schizonepeta tenuifolia, Scutellaria baicalensis, Glycyrrhiza uralensis, Mentha arvensis, Cordyceps cicadae. We examined the immunological effect of SCT in vitro. We studied about the effect of SCT on Th cells' differentiation. In the case of CD4 T cells under neutral condition where there was only rIL-2 stimulus, SCT inhibited IFN-γ secretion by 70-80 %. Likewise, SCT also inhibited the IL-4 secretion of neutral Th cells by 85-90 %. We also experimented with the polarized Th1 cells/ Th2 cells and their production of IFN-γ and IL-4, respectively. There also were inhibitory effects on the polarized cells like there was on neutral cells, they were not as strong on the polarized cells. Under Th1 polarized condition, SCT acted dose-dependently, while in Th2 cells, the IL-4 production was inversely proportional to the doses of SCT. From the current study, it can be concluded that SCT exerts inhibitory effects on cytokine production without interfering with immune cells' activity. The result that SCT inhibits IFN-γ and IL-4 confirms that it does have a effect on immunomodulation.

Immunomodulatory effect of canine periodontal ligament stem cells on allogenic and xenogenic peripheral blood mononuclear cells

  • Kim, Hak-Sung;Kim, Kyoung-Hwa;Kim, Su-Hwan;Kim, Young-Sung;Koo, Ki-Tae;Kim, Tae-Il;Seol, Yang-Jo;Ku, Young;Rhyu, In-Chul;Chung, Chong-Pyoung;Lee, Yong-Moo
    • Journal of Periodontal and Implant Science
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    • v.40 no.6
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    • pp.265-270
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    • 2010
  • Purpose: The aim of this study was to investigate the immunomodulatory effects of canine periodontal ligament stem cells on allogenic and xenogenic immune cells in vitro. Methods: Mixed cell cultures consisting of canine stem cells (periodontal ligament stem cells and bone marrow stem cells) and allogenic canine/xenogenic human peripheral blood mononuclear cells (PBMCs) were established following the addition of phytohemagglutinin. The proliferation of PBMCs was evaluated using the MTS assay. The cell division of PBMCs was analyzed using the CFSE assay. The apoptosis of PBMCs was assessed using the trypan blue uptake method. Results: Periodontal ligament stem cells and bone marrow stem cells inhibited the proliferation of allogenic and xenogenic PBMCs. Both periodontal ligament stem cells and bone marrow stem cells suppressed the cell division of PBMCs despite the existence of a mitogen. No significant differences in the percentages of apoptotic PBMCs were found among the groups. Conclusions: Canine periodontal ligament stem cells have an immunomodulatory effect on allogenic and xenogenic PBMCs. This effect is not a product of apoptosis of PBMCs but is caused by the inhibition of cell division of PBMCs.

Antitumor and Immunomodulatory Activities of Platycodon grandiflorum (길경(桔梗)이 면역활성(免疫活性) 및 항암(抗癌)에 미치는 영향)

  • Lee, Ji-Yung;Lee, Jin-Moo;Lee, Chang-Hoon;Cho, Jung-Hoon;Jang, Jun-Bock;Lee, Kyung-Sub
    • The Journal of Korean Obstetrics and Gynecology
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    • v.23 no.4
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    • pp.10-19
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    • 2010
  • Methods: Intravenous administration of Platycodon grandiflorum was performed 2 days before tumor inoculation, then mice were killed 14 days after tumor inoculation, then number of tumor colonies were counted. Methanol extracts of Platycodon grandiflorum was added to colon26-M3.1 carcinoma cells, L5178Y-R lymphoma cells and Hela cells, and then cell growth was counted. To observe the immunomodulating effects of Platycodon grandiflorum, production of IL-6, IL-10, IL-12 and TNF-$\alpha$ were measured with ELISA assay and the cell growth of macrophage were also counted. Furthermore, antimetastatic experiment after depletion NK cells by injection of anti-asialo GM1 serum was also administered. Results: Intravenous administration of Platycodon grandiflorum significantly inhibited metastasis of colon26-M3.1 carcinoma cells. In an in vitro cytotoxicity analysis, Platycodon grandiflorum affected tumor cell growth above specific concentration. As compared with control, the production of IL-6, IL-10, IL-12 and TNF-$\alpha$ were incresed. And depletion NK cell completly abolished the inhibitory effect of metastasis. Conclusion: Platycodon grandiflorum appears to have considerable activity on immunomodulating effects and inhibit the metastasis of tumor. Further evaluation is needed for settling this.

Role of Prostaglandin E in Modulating Immune Response in Lymph Nodes Draining the Uterus during the Implantation Period in Rats (흰쥐의 착상기간 중 DLN(lymph nodes draining the uterus) Lymphocyte의 활성도에 미치는 Prostaglandin E의 영향)

  • Cho, Hye-Seong;Ryu, Kyung-Za;Kim, Chang-Mee
    • The Korean Journal of Pharmacology
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    • v.25 no.1
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    • pp.93-99
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    • 1989
  • In our previous studies, it was found that activities of maternal peripheral lymphocytes and thymocytes were depressed during the implantation period in rats and rabbits. This study was therefore attempted to clarify further this immunosuppression locally by determining lymphocyte response in lymph nodes draining the uterus (DLN) and to elucidate the mechanism by which prostaglandin E (PGE) modulates immune response during the implantation process in rats. As compared with non-pregnant rats, the response of DLN lymphocytes to concanavalin A (Con A) was depressed during the implantation period in 100% of rats studied. The activity of DLN lymphocytes depressed on day 8 of pregnancy was, however, restored partially by the treatment of indomethacin (ID), indicating that prostaglandin (PG) might be one of factors responsible for immunomodulation during the process of implantation. DLN lymphocyte activity in non-pregnant rats was suppressed if PGE was pre-treated prior to Con A and this suppression was partially restored by the treatment of ID. Furthermore, DLN lymphocytes pre-treated with PGE produced PGE in vitro and this PGE production was blocked by the treatment of ID, suggesting that PGE induced PGE-producing cells. However, the pretreatment of estradiol, progesterone, and hCG at doses enough to suppress lymphocyte activity was ineffective in inducing PGE-producing cells. From these results, it is suggested that PGE induces PGE-producing suppressor cells, thereby increasing PGE concentration and PGE in turn depresses maternal local immune response as well as systemic immune response during the implantation period in rats.

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Effects of β-Glucan from Paenibacillus polymyxa and L-theanine on Growth Performance and Immunomodulation in Weanling Piglets

  • Hwang, Y.H.;Park, B.K.;Lim, J.H.;Kim, M.S.;Song, I.B.;Park, S.C.;Jung, H.K.;Hong, J.H.;Yun, H.I.
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.12
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    • pp.1753-1759
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    • 2008
  • Forty weanling piglets ($5.6{\pm}0.5kg$ and 26 to 30 d of age) were used in a 28-d experiment to determine the effects of ${\beta}$-glucan from Paenibacillus polymyxa and L-theanine on growth performance. Piglets were randomly allotted to four groups (n = 10, 2 animals per pen) provided with the basal feed (control), ${\beta}$-glucan 400 mg/kg feed, L-theanine 80 mg/kg feed or ${\beta}$-glucan plus l-theanine (combination of the above-mentioned concentrations). Body weight and feed consumption were recorded during four weeks. Subsequently, the immunomodulatory effects of ${\beta}$-glucan and L-theanine were investigated for lipopolysaccharide (LPS)-induced cytokine production in vitro and in vivo on day 28. Although there were no significant differences in the growth performances among the treatment groups, ${\beta}$-glucan plus L-theanine had 5.6% greater ADG (p = 0.074) on day 21 to 28. ${\beta}$-Glucan alone or plus L-theanine increased interleukin (IL)-10 levels and decreased interferon (IFN)-$\gamma$ and tumor necrosis factor (TNF)-${\alpha}$ levels in cultured medium by LPS treatment (p<0.05). Plasma IL-10 levels were also increased in the piglets fed with ${\beta}$-glucan alone or plus L-theanine after LPS challenge ($25{\mu}g/kg$, i.p.), whereas plasma IFN-$\gamma$ and TNF-${\alpha}$ levels were decreased (p<0.05). The levels of IFN$\gamma$ in piglets fed with ${\beta}$-glucan plus L-theanine showed the greatest inhibition after LPS challenges. In conclusion, treatment of ${\beta}$-glucan alone or plus L-theanine might lessen inflammatory responses against Gram-negative bacterial infection via the inhibition of pro-inflammatory cytokine production and enhancement of anti-inflammatory cytokine production. Further studies are needed to determine an optimal concentration of ${\beta}$-glucan and L-theanine for improved growth performance.

Bioactive Molecules Produced by Probiotics to Control Enteric Pathogens (프로바이오틱스가 생산하는 생리활성 물질의 장내 유해균 억제 효과)

  • Lim, Kwang-Sei;Griffiths, Mansel W.;Park, Dong June;Oh, Sejong
    • Journal of Dairy Science and Biotechnology
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    • v.32 no.2
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    • pp.141-145
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    • 2014
  • There is a burgeoning number of products on the market that contain probiotics, but do they do you any good? What exactly are probiotics? They have been defined as living organisms that, when ingested in sufficient quantities, provide health benefits beyond basic nutrition. They are often referred to as "friendly bacteria" or "good bacteria." Probiotics have been claimed, amongst other things, to (i) reduce the incidence of colon cancer and other diseases of the colon, such as IBS, (ii) stimulate the immune system, (iii) have anti-hypertensive and anti-cholesterolemic properties, (iv) mitigate against the effect of antibiotics on the intestinal microbiota, and (v) protect against gastrointestinal infections. However, the scientific basis for many of these claims is not well-established. Indeed, the European Food Safety Authority has denied the use of several health claims associated with probiotics, particularly those related to mitigation of diarrhea following consumption of antibiotics. Thus, there is a need for research on the mechanisms of action of probiotics. We have been mainly interested in the use of probiotics to control enteric infections. There are several possible modes of action to explain how probiotics may protect the host from enteric pathogens, including competitive exclusion and immunomodulation. We have shown that probiotics produce bioactive molecules that interfere with bacterial cell-cell communication (also called quorum sensing), and this results in a down-regulation of virulence genes that are responsible for attachment of the pathogen to the gastrointestinal epithelium. These bioactive molecules act on a variety of bacteria, including enterohemorrhagic and enterotoxigenic Escherichia coli, Salmonella, Clostridium difficile and Clostridium perfringens, and there is evidence that they can inhibit the formation of biofilms by Listeria monocytogenes. These bioactive molecules, which are peptidic in nature, can exert their effects not only in vitro but also in vivo, and we have shown that they mitigate against E. coli O157:H7 and Salmonella in mice and Salmonella and E. coli K88 infections in pigs. They can be delivered in foods such as yoghurt and maintain their activity.

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Immuno-stimulating and Antitumor Effects on Mouse Sarcoma 180 by Crude Polysaccharides Extracted from Fruiting Body of Hericium erinaceus (노루궁뎅이(Hericium erinaceus) 자실체 추출 조다당류의 생쥐 Sarcoma 180에 대한 면역증강 및 항암 효과)

  • Choi, Yon-Il;Lee, Jae-Seong;Lee, U-Youn;Lee, Tae-Soo
    • Journal of Life Science
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    • v.20 no.4
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    • pp.623-631
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    • 2010
  • Hericium erinaceus, an edible and medicinal mushroom belonging to the Basidiomycota family, has been used for curing gastric ulcers and stomach cancers in human beings and is also known to have good inhibitory effects on sarcoma 180 and Ehrlich carcinoma in mice. Neutral saline soluble (0.9% NaCl), hot water soluble and methanol soluble substances (hereinafter referred to as Fr. NaCl, Fr. HW and Fr. MeOH, respectively) were extracted from the fruiting body of the mushroom. In in vitro cytotoxicity tests, crude polysaccharides were not cytotoxic against cell lines such as Sarcoma 180, HepG2, HT-29 and NIH3T3 at concentrations of $10{\sim}2,000\;{\mu}g/ml$. Intraperitoneal injection with crude polysaccharides exhibited a life prolongation effect of 29.1~54.1% in mice previously inoculated with Sarcoma 180. Fr. Na increased the numbers of spleen cells by 2.9 fold at a concentration of $50\;{\mu}g/ml$ compared with the control. Fr. Na improved the immuno-potentiating activity of B lymphocytes by increasing alkaline phosphatase activity by 5.5 fold compared with the control at a concentration of $200\;{\mu}g/ml$. Fr. NaCl increased the numbers of peritoneal exudate cells and circulating leukocytes by 4 and 2.3 folds at a concentration of 50 mg/kg, respectively. Therefore, the crude polysaccharides extracted from the fruiting body of H. erinaceus could improve antitumor activities in mice.

Chemical Characteristics and Immunostimulating Activity of Crude Polysaccharide Isolated from Commercial Instant Coffee (시판 인스턴트 커피에서 추출한 다당류의 화학적 특성 및 면역활성)

  • Kwak, Bong-Shin;Shin, Kwang-Soon
    • Korean Journal of Food Science and Technology
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    • v.48 no.3
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    • pp.289-295
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    • 2016
  • To elucidate the new biologically active ingredient in commercial instant coffee, a crude polysaccharide (ICP-0) was isolated by ethanol precipitation, and its immunostimulatory activity was estimated. ICP-0 mainly consisted of galactose (55.5%), mannose (25.7%), arabinose (6.0%), and galacturonic acid (10.1%), suggesting the possibility of its existence as a mixture of galactomannan or pectic polysaccharide. ICP-0 showed proliferative activity in peritoneal macrophages and splenocytes. ICP-0 dose-dependently augmented the production of nitric oxide and reactive oxygen species by peritoneal macrophages. In addition, murine peritoneal macrophages stimulated by ICP-0 showed enhanced production of various cytokines (tumor necrosis factor-${\alpha}$, interleukin-6, and interleukin-12) as compared to unstimulated murine peritoneal macrophages. In an in vitro assay for assessing intestinal immunomodulation, the ICP-0-treated Peyer's patch cells showed higher bone marrow cell proliferation activity at $100{\mu}g/mL$ and higher production of granulocyte-macrophage colony-stimulating factor, compared to the untreated Peyer's patch cells. These results suggest that polysaccharides in commercial instant coffee have a potentiality for macrophage functions and the intestinal immune system.