Honokiol inhibits LPS‐induced maturation and inflammatory response of human monocyte‐derived dendritic cells

Abstract

Honokiol (HNK) is a phenolic compound isolated from the bark of houpu (Magnolia officinalis), a plant widely used in traditional Chinese and Japanese medicine. While substantial evidence indicates that HNK possesses anti-inflammatory activity, its effect on dendritic cells (DCs) during the inflammatory reaction remains unclear. The present study investigates how HNK affects lipopolysaccharide (LPS)-stimulated human monocyte-derived DCs. Our experimental results show that HNK inhibits the inflammatory response of LPS-induced DCs by (1) suppressing the expression of CD11c, CD40, CD80, CD83, CD86, and MHC-II on LPS-activated DCs, (2) reducing the production of TNF-α, IL-1β, IL-6, and IL-12p70 but increasing the production of IL-10 and TGF-β1 by LPS-activated DCs, (3) inhibiting the LPS-induced DC-elicited allogeneic T-cell proliferation, and (4) shifting the LPS-induced DC-driven Th1 response toward a Th2 response. Further, our results show that HNK inhibits the phosphorylation levels of ERK1/2, p38, JNK1/2, IKKα, and IκBα in LPS-activated DCs. Collectively, the findings show that the anti-inflammatory actions of HNK on LPS-induced DCs are associated with the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways.

Immature Dendritic Cells Generated from Cryopreserved Human Monocytes Show Impaired Ability to Respond to LPS and to Induce Allogeneic Lymphocyte Proliferation

“…Having shown that crp-CD14 + cells differentiate into imdDCs, the ability of these cells to respond to an inflammatory stimulus (LPS, a TLR4 ligand that induces the expression of mdDC maturation markers and cytokines/chemokines production) was analyzed [20], [21]. Crp- and frh-imdDCs (5×10 5 viable cells based on Trypan Blue exclusion assay) were treated with LPS and analyzed for the expression of activation markers (CD40, CD80, CD83 and CD86) at 0, 6, 24 and 48 hours post-treatment (hpt) [22].…”

Leukotriene C4 prevents the complete maturation of murine dendritic cells and modifies interleukin-12/interleukin-23 balance

“…The partial or complete reversal of production of IL-12p70 by LPS-activated DCs has been linked to stimuli as diverse as prostaglandins, histamine, alkaloids and phenolic products. [58][59][60][61] In relation to CysLT, in terms of cytokines, the results are contradictory. Machida et al 40 described in Derf-pulsed DCs from bone marrow precursors how antagonists of CysLTR1 led to the enhancement of IL-12p40 while IL-10 was inhibited.…”

The diverging roles of dendritic cells in kidney allotransplantation

“…In murine models, adoptive transfusions of tolerogenic DCs could obtain an expansion of Tregs and reduced allotransplant sensitization in different types of transplants [63][64][65]. Other approaches explored in animal models comprised the inhibition of DCs maturation with agents such as vascular-endothelial growth factor [66], IL-10 [67], laquinimoid [68], shikonin [69], honokiol [70], immunoglobulins [71] and phosphodiesterase inhibitors [72]. Alternatively, drugs favoring the production of Tregs have been employed.…”