All-Trans Retinoic Acid Enhances Bacterial Flagellin-Stimulated Proinflammatory Responses in Human Monocyte THP-1 Cells by Upregulating CD14

Abstract

All-trans retinoic acid (ATRA), an active form of vitamin A, exerts immunomodulatory functions. In this study, we examined the immune potentiating effect of ATRA on bacterial flagellin-induced NF-κB activation and proinflammatory cytokine production in human monocytic cell line THP-1. ATRA treatment significantly enhanced the flagellin-induced NF-κB/AP-1 activity in THP-1 via the RAR/RXR pathway. Similarly, ATRA enhanced the expression and production of TNF-α and IL-1β in THP-1 cells upon flagellin challenge. The cell surface expression of toll-like receptor 5 (TLR5), which is the receptor for bacterial flagellin, was significantly reduced by ATRA in a concentration- and time-dependent manner. To determine the mechanisms underlying the ATRA-enhanced immune response against bacterial flagellin despite the reduced cell surface expression of TLR5 in ATRA-treated THP-1, we examined the cell surface expression of CD14, which has been proposed to be a TLR co-receptor that enhances the response to microbial components. The cell surface expression of CD14 was significantly enhanced by ATRA treatment, especially in the presence of flagellin. Anti-CD14 antibody treatment prior to ATRA and flagellin treatments completely abolished ATRA-enhanced TNF-α and IL-1β production. Our results suggest that ATRA enhances flagellin-stimulated proinflammatory responses in human monocyte THP-1 cells by upregulating CD14 in a RAR/RXR-dependent manner.

Human Glioma Cells Therapy Using ATRA-Induced Differentiation Method to Promote the Inhibitive Effect of TMZ and CCDP

“…ATRA could induce cancer cells to differentiate close to normal cells, restores their lost functions, makes cell less malignant, and increases the sensitivity to chemotherapy drugs. ATRA also has immunomodulatory effects, which can promote the proliferation of immune cells and enhance the killing power of immune cells against tumor cells [5]. ATRA is the clinical treatment for acute promyelocytic leukemia (APL), myelodysplasia, and other hematological malignant diseases and has good performance in dermatology, solid tumors, and vascular-related diseases [6].…”

All-trans Retinoic Acid Induces Expression and Secretion of Carboxypeptidase D in THP-1 Cells

“…In the present study, pretreatment of THP-1 cells with dexamethasone significantly inhibited the ATRA-induced expression and secretion of CPD. Since it is known that ATRA can induce NF-κB activation in THP-1 cells (Hoang et al, 2019), resulting in CPD expression (Koirala et al, 2014), and that dexamethasone suppresses NF-κB activity in THP-1 cells (Steer et al, 2000), we suggest that the inhibitory action of dexamethasone on ATRA-induced CPD expression and secretion may be due to a suppressive effect on NF-κB activation.…”

Fibronectin Functions as a Selective Agonist for Distinct Toll-like Receptors in Triple-Negative Breast Cancer

“…Further studies are needed to understand what role they may play in regulating the TLR-mediated immune response to FnEDA. Interestingly, trans retinoic acid has been shown to enhance the TLR5 immune response to flagellin through the upregulation of CD14 [94].…”