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

Biomed Res Int. 2019 Dec 26:2019:8059312. doi: 10.1155/2019/8059312. eCollection 2019.

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.

MeSH terms

  • Flagellin / toxicity
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / pathology
  • Interleukin-1beta / genetics
  • Lipopolysaccharide Receptors / genetics*
  • Monocytes / drug effects*
  • Monocytes / pathology
  • NF-kappa B / genetics
  • Receptors, Retinoic Acid / genetics
  • Retinoid X Receptors / genetics
  • Signal Transduction / drug effects
  • THP-1 Cells
  • Toll-Like Receptor 5 / genetics
  • Tretinoin / pharmacology*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Interleukin-1beta
  • Lipopolysaccharide Receptors
  • NF-kappa B
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • TLR5 protein, human
  • Toll-Like Receptor 5
  • Tumor Necrosis Factor-alpha
  • Flagellin
  • Tretinoin