Abstract
Geranylgeraniol (GGOH), a natural isoprenoid found in plants, has anti-inflammatory effects via inhibiting the activation of nuclear factor-kappa B (NFκB). However, its detailed mechanism has not yet been elucidated. Recent studies have revealed that isoprenoids can modulate signaling molecules in innate immune responses. We found that GGOH decreased the expression of lipopolysaccharide (LPS)-induced inflammatory genes in human macrophage-like THP-1 cells. Furthermore, we observed that the suppression of NFκB signaling proteins, in particular interleukin-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), occurred in GGOH-treated cells prior to LPS stimulation, suggesting an immunomodulatory effect. These results indicate that GGOH may modulate and help prevent excessive NFκB activation that can lead to numerous diseases.
Highlights
Nuclear factor-kappa B (NFκB) is a stress-responsive transcription factor involved in various cellular events, including cell proliferation, differentiation, carcinogenesis, autophagy, neurodegeneration, and acute and chronic inflammation [1,2,3,4,5,6,7,8,9]
We observed that the pretreatment of GGOH for 24 h suppressed LPS-induced interleukin-6 (IL-6) expression in differentiated THP-1 cells
GGOH decreased the mRNA levels of C-C motif chemokine ligand 2 (CCL2) and cyclooxygenase-2 (COX2), which are regulated by NFκB (Figure 1D,E)
Summary
Nuclear factor-kappa B (NFκB) is a stress-responsive transcription factor involved in various cellular events, including cell proliferation, differentiation, carcinogenesis, autophagy, neurodegeneration, and acute and chronic inflammation [1,2,3,4,5,6,7,8,9]. Activated NFκB in the cytoplasm translocates into the nucleus and stimulates the expression of its numerous target genes. The enhancement of mRNA expression of NFκB target genes is physiologically necessary as a response to various types of stress; excessive, continuous expression of these mRNAs is associated with several diseases. The activation of NFκB, mediated by toll-like receptor 4 (TLR4), is involved in an acute inflammatory response, and in the chronic, low-grade inflammation that can induce metabolic syndrome [10]. Numerous papers have indicated that plants produce effective secondary metabolites for the inactivation and suppression of TLR4-mediated NFκB activation [12]. Such ingredients are contained in our daily consumed foods. Epigallocatechin-3-gallate in green tea can inhibit the TLR4–NFκB signal transduction axis [13]
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