Sulforaphane, a naturally occurring isothiocyanate, exhibits anti-inflammatory effects by targeting GSK3β/Nrf-2 and NF-κB pathways in T cells

• Published in: Journal of functional foods Vol. 19; pp. 426 - 438
• Main Authors: Checker, Rahul, Gambhir, Lokesh, Thoh, Maikho, Sharma, Deepak, Sandur, Santosh K.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.12.2015; Elsevier
• Subjects: Cytokines; GSH/GSSG; GSK3β; Homeostatic proliferation; ROS; GSK3β; Cytokines; Homeostatic proliferation; GSH/GSSG; ROS
• ISSN: 1756-4646; 2214-9414
• DOI: 10.1016/j.jff.2015.08.030

•SF suppressed mitogen induced T and B-cell proliferation and cytokine secretion.•SF increased basal ROS levels and depleted GSH/GSSG ratio in lymphocytes.•Thiol antioxidants but not SOD/catalase abrogated SF mediated immunosuppression.•SF induced phosphorylation of PI3K/AKT leading to inactivation of GSK3β.•SF activated Nrf-2 and prevented direct interaction between NF-κB and DNA. 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.