Kaempferol Suppresses the Activation of Mast Cells by Modulating the Expression of FcεRI and SHIP1

Abstract

In the present study, we evaluated the effects of kaempferol on bone marrow-derived mast cells (BMMCs). Kaempferol treatment significantly and dose-dependently inhibited IgE-induced degranulation, and cytokine production of BMMCs under the condition that cell viability was maintained. Kaempferol downregulated the surface expression levels of FcεRI on BMMCs, but the mRNA levels of FcεRIα, β, and γ-chains were not changed by kaempferol treatment. Furthermore, the kaempferol-mediated downregulation of surface FcεRI on BMMCs was still observed when protein synthesis or protein transporter was inhibited. We also found that kaempferol inhibited both LPS- and IL-33-induced IL-6 production from BMMCs, without affecting the expression levels of their receptors, TLR4 and ST2. Although kaempferol treatment increased the protein amount of NF-E2-related factor 2 (NRF2)—a master transcription factor of antioxidant stress—in BMMCs, the inhibition of NRF2 did not alter the suppressive effect of kaempferol on degranulation. Finally, we found that kaempferol treatment increased the levels of mRNA and protein of a phosphatase SHIP1 in BMMCs. The kaempferol-induced upregulation of SHIP1 was also observed in peritoneal MCs. The knockdown of SHIP1 by siRNA significantly enhanced IgE-induced degranulation of BMMCs. A Western blotting analysis showed that IgE-induced phosphorylation of PLCγ was suppressed in kaempferol-treated BMMCs. These results indicate that kaempferol inhibited the IgE-induced activation of BMMCs by downregulating FcεRI and upregulating SHIP1, and the SHIP1 increase is involved in the suppression of various signaling-mediated stimulations of BMMCs, such as those associated with TLR4 and ST2.

Kaempferol exerts anti-inflammatory effects by accelerating Treg development via AhR-mediated and PU.1/IRF4-dependent transactivation of theAldh1a2/RALDH2 gene in dendritic cells

“…Kaempferol and other flavonoids including quercetin, luteolin, and nobiletin, are the most vigorously studied polyphenols due to their beneficial effects in the host body, such as anticancer and anti-obesity activities. Previous studies, including ours, reported the anti-allergic effects of flavonoids targeting mast cells (2–8). Quercetin and luteolin, but not kaempferol, were recently identified as activators of the Aldh1a2 promoter in an assay using the human monocyte cell line THP-1 carrying a reporter plasmid (9).…”

Supplementing broiler diets with bacterial selenium nanoparticles enhancing performance, carcass traits, blood indices, antioxidant status, and caecal microbiota of Eimeria tenella-infected broiler chickens

“…This anti-inflammatory action may be caused by active compounds in SeNPs and their precursors ( Abdel-Moneim et al, 2022 ). In addition to immunomodulatory and anti-inflammatory properties, it can prevent the production of proinflammatory cytokines ( Attia et al, 2020 , Nagata et al, 2023 ), according to previous studies. Apoptosis may influence the chicks' response to particular intracellular parasite infections and promote the removal of damaged or contaminated cells ( Al-Quraishy et al, 2019 ).…”

Codium fragile Suppressed Chronic PM2.5-Exposed Pulmonary Dysfunction via TLR/TGF-β Pathway in BALB/c Mice

“…Codium fragile also inhibited inflammatory cytokines such as TNF-α, IL-1β, and IL-6 and nuclear translocation of NF-κB by suppressing the phosphorylation and degradation of IκB-α [ 34 ], and suppressed inflammatory indicators such as COX-2, iNOS, prostaglandin E2, and release of nitric oxide (NO) [ 35 ]. In addition, treatment of kaempferol, as one of the flavonoid compounds, significantly inhibited IgE and lipopolysaccharide-induced inflammation via nuclear factor erythroid 2-related factor 2 (Nrf2)/SHIP1 on bone marrow-derived mast cells (BMMCs) [ 36 ]. In various previous studies, Codium fragile might help significantly inhibit the inflammatory reaction caused by PM 2.5 , and in particular, it is judged to be able to suppress inflammation through the NF-kB pathway.…”