Sulforaphane, a naturally occurring isothiocyanate, exhibits anti-inflammatory effects by targeting GSK3β/Nrf-2 and NF-κB pathways in T cells
A potent Nrf-2 activator sulforaphane (SF), which is currently under clinical trials for cancer therapy, was employed to elucidate the role of Keap1/Nrf-2/ARE signalling pathway in T-cell responses. SF suppressed mitogen induced T-cell and B-cell proliferation. It also inhibited mitogen induced upre...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-12-01
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| Series: | Journal of Functional Foods |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464615004156 |
| _version_ | 1819060679561183232 |
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| author | Rahul Checker Lokesh Gambhir Maikho Thoh Deepak Sharma Santosh K. Sandur |
| author_facet | Rahul Checker Lokesh Gambhir Maikho Thoh Deepak Sharma Santosh K. Sandur |
| author_sort | Rahul Checker |
| collection | DOAJ |
| description | A potent Nrf-2 activator sulforaphane (SF), which is currently under clinical trials for cancer therapy, was employed to elucidate the role of Keap1/Nrf-2/ARE signalling pathway in T-cell responses. SF suppressed mitogen induced T-cell and B-cell proliferation. It also inhibited mitogen induced upregulation of T-cell (CD25 and CD69) and B-cell (CD80 and CD86) activation markers and suppressed secretion of cytokines (IL-2, IL-4, IL-6 and IFN-γ). SF induced oxidative stress and its anti-inflammatory effects were abrogated by thiol antioxidants. SF activated PI3K/AKT, leading to phosphorylation mediated suppression of GSK3β resulting in Nrf-2 activation. We also show for the first time that SF can prevent direct interaction between NF-κB and its consensus sequence by modulating thiol groups. It also suppressed homeostatic proliferation of T-cells and suppressed lipopolysaccharide induced pro-inflammatory mediators in macrophages. Our study shows that the potent anti-inflammatory effects of SF are mediated via modulation of PI3K/AKT/GSK3β/Nrf-2 and NF-κB pathway in T-cells. |
| first_indexed | 2024-12-21T14:30:50Z |
| format | Article |
| id | doaj.art-18b5b8b0b71f477a91e894bc57922117 |
| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-12-21T14:30:50Z |
| publishDate | 2015-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-18b5b8b0b71f477a91e894bc579221172022-12-21T19:00:29ZengElsevierJournal of Functional Foods1756-46462015-12-0119426438Sulforaphane, a naturally occurring isothiocyanate, exhibits anti-inflammatory effects by targeting GSK3β/Nrf-2 and NF-κB pathways in T cellsRahul Checker0Lokesh Gambhir1Maikho Thoh2Deepak Sharma3Santosh K. Sandur4Radiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Mumbai, IndiaRadiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Mumbai, IndiaRadiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Mumbai, IndiaRadiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Mumbai, IndiaCorresponding author. Radiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Modular Laboratories, Trombay, Mumbai 400085, India. Tel.: +91 22 25595356; fax: +91 22 25505326.; Radiation Biology & Health Sciences Division, Bio-Science Group, Bhabha Atomic Research Centre, Mumbai, IndiaA potent Nrf-2 activator sulforaphane (SF), which is currently under clinical trials for cancer therapy, was employed to elucidate the role of Keap1/Nrf-2/ARE signalling pathway in T-cell responses. SF suppressed mitogen induced T-cell and B-cell proliferation. It also inhibited mitogen induced upregulation of T-cell (CD25 and CD69) and B-cell (CD80 and CD86) activation markers and suppressed secretion of cytokines (IL-2, IL-4, IL-6 and IFN-γ). SF induced oxidative stress and its anti-inflammatory effects were abrogated by thiol antioxidants. SF activated PI3K/AKT, leading to phosphorylation mediated suppression of GSK3β resulting in Nrf-2 activation. We also show for the first time that SF can prevent direct interaction between NF-κB and its consensus sequence by modulating thiol groups. It also suppressed homeostatic proliferation of T-cells and suppressed lipopolysaccharide induced pro-inflammatory mediators in macrophages. Our study shows that the potent anti-inflammatory effects of SF are mediated via modulation of PI3K/AKT/GSK3β/Nrf-2 and NF-κB pathway in T-cells.http://www.sciencedirect.com/science/article/pii/S1756464615004156CytokinesGSH/GSSGROSGSK3βHomeostatic proliferation |
| spellingShingle | Rahul Checker Lokesh Gambhir Maikho Thoh Deepak Sharma Santosh K. Sandur Sulforaphane, a naturally occurring isothiocyanate, exhibits anti-inflammatory effects by targeting GSK3β/Nrf-2 and NF-κB pathways in T cells Journal of Functional Foods Cytokines GSH/GSSG ROS GSK3β Homeostatic proliferation |
| title | Sulforaphane, a naturally occurring isothiocyanate, exhibits anti-inflammatory effects by targeting GSK3β/Nrf-2 and NF-κB pathways in T cells |
| title_full | Sulforaphane, a naturally occurring isothiocyanate, exhibits anti-inflammatory effects by targeting GSK3β/Nrf-2 and NF-κB pathways in T cells |
| title_fullStr | Sulforaphane, a naturally occurring isothiocyanate, exhibits anti-inflammatory effects by targeting GSK3β/Nrf-2 and NF-κB pathways in T cells |
| title_full_unstemmed | Sulforaphane, a naturally occurring isothiocyanate, exhibits anti-inflammatory effects by targeting GSK3β/Nrf-2 and NF-κB pathways in T cells |
| title_short | Sulforaphane, a naturally occurring isothiocyanate, exhibits anti-inflammatory effects by targeting GSK3β/Nrf-2 and NF-κB pathways in T cells |
| title_sort | sulforaphane a naturally occurring isothiocyanate exhibits anti inflammatory effects by targeting gsk3β nrf 2 and nf κb pathways in t cells |
| topic | Cytokines GSH/GSSG ROS GSK3β Homeostatic proliferation |
| url | http://www.sciencedirect.com/science/article/pii/S1756464615004156 |
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