Vitamin A differentially regulates cytokine expression in respiratory epithelial and macrophage cell lines

Rhiannon R Penkert1, Bart G Jones1, Hans Häcker1

  • 1Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.

Cytokine
|December 13, 2016
PubMed

Insights

Vitamin A metabolite retinoic acid affects respiratory cells differently. It downregulates IL-6 in epithelial cells but upregulates it in macrophages, impacting immune responses and explaining past study contradictions.

Area of Science:

  • Immunology
  • Nutritional Science
  • Cell Biology

Background:

  • Vitamin A is crucial for children's respiratory health and immune function.
  • Vitamin A's effects on immune responses, like IL-6 regulation, appear contradictory in different contexts.
  • Retinoic acid (RA), a vitamin A metabolite, is investigated for its role in immune modulation.

Purpose of the Study:

  • To investigate the cell-specific effects of retinoic acid (RA) on respiratory tract epithelial cells (LETs) and macrophages (MACs).
  • To resolve apparent contradictions in how vitamin A influences immune responses, particularly IL-6 production.
  • To understand the impact of RA on immune cell signaling pathways relevant to respiratory infections.

Main Methods:

  • Utilized cell line models of respiratory tract epithelial cells (LETs) and macrophages (MACs).
  • Exposed cell lines to lipopolysaccharide (LPS) or Sendai virus to mimic respiratory pathogen exposure.
  • Analyzed the effects of retinoic acid (RA) on gene and protein expression, including IL-6, MCP-1, GMCSF, IL-10, and RARβ transcripts.

Main Results:

  • Retinoic acid (RA) downregulated IL-6 in epithelial cells (LETs) but upregulated it in macrophages (MACs) upon stimulation.
  • RA increased transcript levels of MCP-1, GMCSF, and IL-10 specifically in macrophages.
  • RA upregulated RARβ transcripts in epithelial cells, suggesting cell-specific metabolic regulation.

Conclusions:

  • The effects of retinoic acid on immune responses are highly dependent on the target cell type.
  • Cell-specific effects of RA help explain discrepancies in previous vitamin A research.
  • Clinical trials involving vitamin A supplementation should consider these cell-specific immune modulations.

Related Concept Videos

Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
17.9K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.0K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.5K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.9K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.8K