Cutting Edge: All-trans Retinoic Acid Down-Regulates TLR2 Expression and Function1

@article{Liu2005CuttingEA,
  title={Cutting Edge: All-trans Retinoic Acid Down-Regulates TLR2 Expression and Function1},
  author={Philip T Liu and Stephan R. Krutzik and Jenny Kim and Robert L. Modlin},
  journal={The Journal of Immunology},
  year={2005},
  volume={174},
  pages={2467 - 2470}
}
A major consequence of microbial infection is the tissue injury that results from the host inflammatory response. In acne, inflammation is due in part to the ability of Propionibacterium acnes to activate TLR2. Because all-trans retinoic acid (ATRA) decreases inflammation in acne, we investigated whether it regulates TLR2 expression and function. Treatment of primary human monocytes with ATRA led to the down-regulation of TLR2 as well as it’s coreceptor CD14, but not TLR1 or TLR4. The ability… 

Figures from this paper

Effects of all-trans retinoic acid on expression of Toll-like receptor 5 on immune cells

It is conceivable that retinoids are required for adequate innate and adaptive immune responses to agents o f infectious diseases and cancers, and understanding the molecular regulatory mechanism of TLR-5 may assist in the design of alternative strategies for the treatment of infectious diseases, leukemia and cancers.

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

The results suggest that ATRA enhances flagellin-stimulated proinflammatory responses in human monocyte THP-1 cells by upregulating CD14 in a RAR/RXR-dependent manner.

Retinol Suppresses the Activation of Toll-Like Receptors in MyD88- and STAT1-Independent Manners

The results showed that retinol suppressed the expression of various inflammatory cytokines in bone marrow-derived macrophages stimulated with ligands of TLR2, TLR3, or TLR4, demonstrating that inhibitory effect ofretinol is not limited to a single TLR.

Vitamin D3 down‐regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen‐associated molecular patterns

The data provide strong evidence that 1,25(OH)2D3 primes monocytes to respond less effectively to bacterial cell wall components in a VDR‐dependent mechanism, most likely due to decreased levels of TLR2 and TLR4.

Convergence of IL-1β and VDR Activation Pathways in Human TLR2/1-Induced Antimicrobial Responses

A novel mechanism of host defense requiring the induction of IL-1β in synergy with vitamin D activation, for the TLR-induced antimicrobial pathway against an intracellular pathogen is identified.

Innate immunity and Toll-like Receptors modulation in acne

The effects of a vegetal natural extract associated with a long chain lipid (TLR2-Regul) in ex vivo human skin in con- tact with P. acnes induced signi# cant increase of IL-8 expression in all untreated skin explants.

Involvement of Pattern Recognition Receptors in the Direct Influence of Bacterial Components and Standard Antiacne Compounds on Human Sebaceous Gland Cells

Microbial components use pattern recognition receptors to directly activate sebocytes to express a wide range of proinflammatory molecules and especially IL-8 and IL-6 in a TLR4- and CD14-specific manner.

All-Trans Retinoic Acid–Triggered Antimicrobial Activity against Mycobacterium tuberculosis Is Dependent on NPC2

Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3 (1,25D3), the biologically active forms of vitamin A and vitamin D, respectively, indicates that ATRA and 1, 25D3 induce mechanistically distinct antimicrobial activities.
...

References

SHOWING 1-10 OF 24 REFERENCES

Review of the Innate Immune Response in Acne vulgaris: Activation of Toll-Like Receptor 2 in Acne Triggers Inflammatory Cytokine Responses

Data suggest that P. acnes triggers inflammatory cytokine responses in acne by activation of TLR2, and that this receptor may provide a novel target for the treatment of this common skin disease.

Differential Effects of a Toll-Like Receptor Antagonist on Mycobacterium tuberculosis-Induced Macrophage Responses1

It is demonstrated that expression of a dominant negative TLR2 or TLR4 proteins in RAW 264.7 macrophages partially blocked Mtb-induced NF-κB activation, and E5531 could substantially block LPS- and Mt b-induced TNF-α production in both RAW 264,7 cells and primary human alveolar macrophage (AMφ).

Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne

Both Propionibacterium acnes and supernatants obtained from 72-h P. acnes cultures could induce significant concentrations of IL-1 beta, TNF-alpha, and IL-8 by both cell lines and by peripheral blood mononuclear cells as determined by enzyme-linked immunosorbent assay.

Activation and regulation of Toll-like receptors 2 and 1 in human leprosy

Investigation in leprosy provides evidence that regulated expression and activation of TLRs at the site of disease contribute to the host defense against microbial pathogens.

Retinoids Inhibit Interleukin-12 Production in Macrophages through Physical Associations of Retinoid X Receptor and NFκB*

It is proposed that retinoid-mediated suppression of the IL-12 production from LPS-activated macrophages may involve both inhibition of the NFκB-DNA interactions and competitive recruitment of transcription integrators betweenNFκB and RXR.

Retinoic Acid Receptor-Mediated Induction of ABCA1 in Macrophages

In macrophages from RARγ−/− mice, TTNPB still induced ABCA1, in association with marked upregulation of RARα, suggesting that high levels of R BARα can compensate for the absence of R ARγ, and a direct role of Rarγ/RXR in induction of macrophage ABCA 1 is indicated.

Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease

In vivo administration of antibody to Tim-3 enhances the clinical and pathological severity of experimental autoimmune encephalomyelitis (EAE), a Th1-dependent autoimmune disease, and increases the number and activation level of macrophages.

Tissue Expression of Human Toll-Like Receptors and Differential Regulation of Toll-Like Receptor mRNAs in Leukocytes in Response to Microbes, Their Products, and Cytokines

Analysis of TLR expression in fractionated primary human leukocytes indicates that professional phagocytes express the greatest variety ofTLR mRNAs although several TLRs appear more restricted to B cells, suggesting additional roles for TLRs in adaptive immunity.

Toll‐like receptors and the host defense against microbial pathogens: bringing specificity to the innate‐immune system

The crucial role of TLRs for the host defense against infections has been strengthened recently by the description of patients partially defective in the TLR‐activation pathways.

Mycobacterial lipoarabinomannan recognition requires a receptor that shares components of the endotoxin signaling system.

The LPS and LAM receptors share CD14, LBP, and a putative endotoxin antagonist-inhibitable signal transducing component, however, the LAM signaling system appears to require an additional receptor component whose expression is restricted to cells of hemopoietic origin.