scholarly journals Anti-allergic and Cytotoxic Effects of Sesquiterpenoids and Phenylpropanoids Isolated from Magnolia biondii

2017 ◽  
Vol 12 (10) ◽  
pp. 1934578X1701201 ◽  
Author(s):  
Thi Tuyet Mai Nguyen ◽  
Thi Thu Nguyen ◽  
Hyun-Su Lee ◽  
Bomi Lee ◽  
Byung Sun Min ◽  
...  
Keyword(s):  
T Cells ◽  
Optical Rotation ◽  
Interleukin 2 ◽  
2D Nmr ◽  
Inhibitory Effect ◽  
2D Nmr Spectroscopy ◽  
Jurkat T Cells ◽  
Cytotoxic Effects ◽  
D 12 ◽  
Mcf 7

Ten sesquiterpenoids (1-10) and six phenylpropanoid derivatives (11-16) were isolated from the flower buds of Magnolia biondii Pamp. Their structures were determined by 1D- and 2D-NMR spectroscopy, mass spectrometry, and optical rotation. To evaluate their anti-allergic properties, the inhibitory effect of each isolate (1-16) on interleukin-2 (IL-2) gene expression was examined in Jurkat T cells. Among the isolated compounds, three sesquiterpenoids (2, 5, and 7) and two monoterpenoids (12 and 13) strongly inhibited IL-2 production in Jurkat T cells. Four compounds, (-)-parthenolide (2), eudesm-4(15)-eno-1β,6α-diol (5), biondinin D (12), and tiliroside (16), showed cytotoxicity against Jurkat T cells. In addition, (-)-parthenolide (2) exhibited cytotoxicity against the human cervical cancer HeLa cell line, the human breast cancer MCF-7, and human promyelocytic leukemia HL-60 cell lines.

scholarly journals Unusual Polyhydroxylated Steroids from the Starfish Anthenoides laevigatus, Collected off the Coastal Waters of Vietnam

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1440
Author(s):  
Alla A. Kicha ◽  
Dinh T. Ha ◽  
Timofey V. Malyarenko ◽  
Anatoly I. Kalinovsky ◽  
Roman S. Popov ◽  
...  
Keyword(s):  
Coastal Waters ◽  
2D Nmr ◽  
2D Nmr Spectroscopy ◽  
Cytotoxic Effects ◽  
One Dimensional ◽  
The Common ◽  
Polyhydroxylated Steroids ◽  
New Compounds ◽  
Ht 29 ◽  
Inhibit Cell Proliferation

Four new polyhydroxylated steroids 1–4 were isolated along with two previously known related steroids 5 and 6 from the methanolic extract of the starfish Anthenoides laevigatus collected off the coastal waters of Vietnam. Structures of new compounds were substantially elucidated by one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy and HRESIMS techniques. Heptaol 1 and hexaol 2 contain the common 5α-cholestane skeleton, while hexaol 3 and heptaol 4 have the rare among starfish steroid compounds 5β-cholestane skeleton. Compounds 1, 5, and 6 do not show cytotoxic effects against normal JB6 Cl41 and cancer HT-29 and MDA-MB-231 cells, however they inhibit cell proliferation and colony formation of cancer HT-29 and MDA-MB-231 cells.

scholarly journals Clausmarin A, Potential Immunosuppressant Revealed by Yeast-Based Assay and Interleukin-2 Production Assay in Jurkat T Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0136804 ◽  
Author(s):  
Pitipreya Suauam ◽  
Boon-ek Yingyongnarongkul ◽  
Tanapat Palaga ◽  
Tokichi Miyakawa ◽  
Chulee Yompakdee
Keyword(s):  
T Cells ◽  
Interleukin 2 ◽  
Jurkat T Cells

scholarly journals Requirement for Transcription Factor NFAT in Interleukin-2 Expression

1999 ◽  
Vol 19 (3) ◽  
pp. 2300-2307 ◽  
Author(s):  
Chi-Wing Chow ◽  
Mercedes Rincón ◽  
Roger J. Davis
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Transcription Factor ◽  
Nuclear Translocation ◽  
Interleukin 2 ◽  
Inhibitory Effect ◽  
Dominant Negative ◽  
Activated T Cells ◽  
Nfat Activation ◽  
Nfat Transcription Factor

ABSTRACT The nuclear factor of activated T cells (NFAT) transcription factor is implicated in expression of the cytokine interleukin-2 (IL-2). Binding sites for NFAT are located in the IL-2 promoter. Furthermore, pharmacological studies demonstrate that the drug cyclosporin A inhibits both NFAT activation and IL-2 expression. However, targeted disruption of the NFAT1 and NFAT2 genes in mice does not cause decreased IL-2 secretion. The role of NFAT in IL-2 gene expression is therefore unclear. Here we report the construction of a dominant-negative NFAT mutant (dnNFAT) that selectively inhibits NFAT-mediated gene expression. The inhibitory effect of dnNFAT is mediated by suppression of activation-induced nuclear translocation of NFAT. Expression of dnNFAT in cultured T cells caused inhibition of IL-2 promoter activity and decreased expression of IL-2 protein. Similarly, expression of dnNFAT in transgenic mice also caused decreased IL-2 gene expression. These data demonstrate that NFAT is a critical component of the signaling pathway that regulates IL-2 expression.

Manganese promotes phorbol ester-induced interleukin-2 production via AP-1 activation in Jurkat T-cells

2012 ◽  
Vol 211 (3) ◽  
pp. 312-318 ◽  
Author(s):  
Susumu Tanaka ◽  
Yasunori Masuda ◽  
Chihiro Honma ◽  
Kohei Hosaka ◽  
Katsunori Takahashi ◽  
...  
Keyword(s):  
T Cells ◽  
Phorbol Ester ◽  
Interleukin 2 ◽  
Jurkat T Cells

scholarly journals Oligomycin inhibits store-operated channels by a mechanism independent of its effects on mitochondrial ATP

1997 ◽  
Vol 324 (3) ◽  
pp. 971-980 ◽  
Author(s):  
Jwa Hwa CHO ◽  
M. BALASUBRAMANYAM ◽  
Galina CHERNAYA ◽  
Jeffrey P. GARDNER ◽  
Abraham AVIV ◽  
...  
Keyword(s):  
T Cells ◽  
Rank Order ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Inhibitory Effect ◽  
Jurkat T Cells ◽  
Ovary Cells ◽  
Atp Production ◽  
Patch Pipette ◽  
Pump Activity

Inhibitors of mitochondrial oxidative metabolism have been proposed to interfere with Ca2+ influx mediated by store-operated channels (SOC), secondary to their effects on ATP production. We assessed SOC activity by 45Ca2+ influx and fluorimetric measurements of free Ca2+ or Mn2+ quench in thapsigargin-treated Chinese hamster ovary cells and Jurkat T-cells, and additionally by electrophysiological measurements of the Ca2+-release-activated Ca2+ current (Icrac) in Jurkat T-cells. Various mitochondrial antagonists were confirmed to inhibit SOC. However, the following evidence supported the proposal that oligomycin, in particular, exerts an inhibitory effect on SOC in addition to its known actions on mitochondria and Na+-pump activity: (i) the concentrations of oligomycin required to inhibit SOC-mediated Ca2+ influx or Icrac (half-inhibitory concentration ∼2 μM) were nearly 50-fold higher than the concentrations that blocked mitochondrial ATP production; (ii) the rank order of potency of oligomycins A, B and C for decreasing SOC-mediated Ca2+ influx or Icrac differed from that known for inhibition of mitochondrial function; (iii) oligomycin blocked Icrac under voltage clamp and with intracellular Na+ and K+ concentrations fixed by dialysis from the patch pipette, arguing that the effect was not secondary to membrane polarization or pump activity; and (iv) fixing the cytosolic ATP concentration by dialysis from the patch pipette attenuated rotenone- but not oligomycin-mediated inhibition of Icrac. Oligomycin also blocked volume-activated Cl- currents, a profile common to some other known blockers of SOC that are not known mitochondrial inhibitors. These findings raise the possibility that oligomycin interacts directly with SOC, and thus may extend the known pharmacological profile for this type of Ca2+-influx pathway.

scholarly journals Costimulation by B7-1 and LFA-3 targets distinct nuclear factors that bind to the interleukin-2 promoter: B7-1 negatively regulates LFA-3-induced NF-AT DNA binding.

1997 ◽  
Vol 17 (3) ◽  
pp. 1314-1323 ◽  
Author(s):  
E Parra ◽  
M Varga ◽  
G Hedlund ◽  
T Kalland ◽  
M Dohlsten
Keyword(s):  
T Cells ◽  
Dna Binding ◽  
Transcriptional Activity ◽  
Interleukin 2 ◽  
Luciferase Reporter ◽  
Jurkat T Cells ◽  
Response Elements ◽  
Nuclear Factors ◽  
Hla Dr ◽  
Nf Kappab

We have characterized the regulation of nuclear factors involved in transcriptional control of the interleukin-2 (IL-2) promoter-enhancer activity in Jurkat T cells stimulated with superantigen presented on HLA-DR transfectants combined with the ligands LFA-3 (CD58) and B7-1 (CD80). Gel shift analyses showed that NF-AT was strongly induced in LFA-3-costimulated Jurkat T cells, suggesting that NF-AT is a key target nuclear factor for the CD2-LFA-3 pathway. Studies using HLA-DR-B7-1-LFA-3 triple transfectants showed that the LFA-3-induced NF-AT DNA binding activity was negatively regulated by B7-1 costimulation. In contrast, induction of a CD28 response complex containing only c-Rel proteins was seen after B7-1 costimulation. Both LFA-3 costimulation and B7-1 costimulation induced the AP-1 and NF-kappaB nuclear factors. Distinct compositions of the NF-AT complexes were seen in B7-1- and LFA-3-costimulated cells. LFA-3 induced primarily Jun-D, Fra-1, and Fra-2, while B7-1 induced June-D-Fos complexes. In contrast, AP-1 and NF-kappaB complexes induced in B7-1- and LFA-3-costimulated T cells showed similar contents. Transient transfection of Jurkat T cells with a construct encoding the IL-2 enhancer-promoter region (position -500 to +60) linked to a luciferase reporter gene revealed that B7-1 costimulation was required to induce strong transcriptional activity. Combined B7-1-LFA-3 costimulation resulted in a synergistic increase in IL-2 transcriptional activity. Multimers of the AP-1, NF-AT, NF-kappaB, and CD28 response elements showed distinct kinetics and activity after LFA-3 and B7-1 costimulation and revealed that B7-1 and LFA-3 converge to superinduce transcriptional activity of the AP-1, NF-AT, and CD28 response elements. Transcriptional studies with an IL-2 enhancer-promoter carrying a mutation in the CD28 response element site revealed that the activity was reduced by 80% after B7-1 and B7-1-LFA-3 costimulation whereas the transcriptional activity induced by LFA-3 was unaffected. Our data strongly suggest a selectivity in induction of nuclear factors by the CD2-LFA-3 and CD28-B7-1 pathways. This selectivity may contribute to regulation of the levels of IL-2 induced by LFA-3 and B7-1 costimulation and favor autocrine and paracrine T-cell responses, respectively.

scholarly journals Loureirin B Exerts its Immunosuppressive Effects by Inhibiting STIM1/Orai1 and KV1.3 Channels

2021 ◽  
Vol 12 ◽  
Author(s):  
Shujuan Shi ◽  
Qianru Zhao ◽  
Caihua Ke ◽  
Siru Long ◽  
Feng Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Molecular Mechanisms ◽  
Cell Model ◽  
Interleukin 2 ◽  
Immunosuppressive Effect ◽  
Dependent Manner ◽  
Jurkat T Cells ◽  
In The Wild ◽  
Resina Draconis ◽  
Loureirin B

Loureirin B (LrB) is a constituent extracted from traditional Chinese medicine Resina Draconis. It has broad biological functions and an impressive immunosuppressive effect that has been supported by numerous studies. However, the molecular mechanisms underlying Loureirin B-induced immune suppression are not fully understood. We previously reported that Loureirin B inhibited KV1.3 channel, calcium ion (Ca2+) influx, and interleukin-2 (IL-2) secretion in Jurkat T cells. In this study, we applied CRISPR/Cas9 to edit KV1.3 coding gene KCNA3 and successfully generated a KV1.3 knockout (KO) cell model to determine whether KV1.3 KO was sufficient to block the Loureirin B-induced immunosuppressive effect. Surprisingly, we showed that Loureirin B could still inhibit Ca2+ influx and IL-2 secretion in the Jurkat T cells in the absence of KV1.3 although KO KV1.3 reduced about 50% of Ca2+ influx and 90% IL-2 secretion compared with that in the wild type cells. Further experiments showed that Loureirin B directly inhibited STIM1/Orai1 channel in a dose-dependent manner. Our results suggest that Loureirin B inhibits Ca2+ influx and IL-2 secretion in Jurkat T cells by inhibiting both KV1.3 and STIM1/Orai1 channels. These studies also revealed an additional molecular target for Loureirin B-induced immunosuppressive effect, which makes it a promising leading compound for treating autoimmune diseases.

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