Effects of all-trans retinoic acid on expression of Toll-like receptor 5 on immune cells.
10.5125/jkaoms.2010.36.6.481
- Author:
Ki Hyung KIM
1
;
Sang Jun PARK
Author Information
1. CK Dental Hospital, Busan, Korea.
- Publication Type:Original Article
- Keywords:
Tretinoin;
Toll-like receptor 5;
Cellular immunity;
NF-kappa B
- MeSH:
Apoptosis;
Binding Sites;
Blotting, Western;
Communicable Diseases;
Flagellin;
Humans;
Immunity, Cellular;
Interleukin-1;
Leukemia;
NF-kappa B;
Pyrrolidines;
Retinoids;
Signal Transduction;
Thiocarbamates;
Toll-Like Receptor 5;
Toll-Like Receptors;
Transcription Factors;
Tretinoin;
Vitamin A
- From:Journal of the Korean Association of Oral and Maxillofacial Surgeons
2010;36(6):481-489
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
INTRODUCTION: TLR-5, a member of the toll-like receptor (TLR) family, is a element of the type I transmembrane receptors, which are characterized by an intracellular signaling domain homolog to the interleukin-1 receptor. These receptors recognize microbial components, particularly bacterial flagellin. All-trans retinoic acid (atRA, tretinoin), a natural metabolite of vitamin A, acts as a growth and differentiation factor in many tissues, and is also needed for immune functions. In this study, THP-1 human macrophage-monocytes were used to examine the mechanisms by which atRA regulated the expression of TLR-5. Because the molecular mechanism underlying this regulation at the transcriptional level is also unclear, this study examined which putative transcription factors are responsible for TLR-5 expression by atRA in immune cells. MATERIALS AND METHODS: This study examined whether atRA induces the expression of TLR-5 in THP-1 cells using reverse transcription-polymerase chain reaction (RT-PCR), and which transcription factors are involved in regulating the TLR-5 promoter in RAW264.7 cells using a reporter assay system. Western blot analysis was used to determine which signal pathway is involved in the expression of TLR-5 in atRA-treated THP-1 cells. RESULTS: atRA at a concentration of 10 nM greatly induced the expression of TLR-5 in THP-1 cells. Human TLR-5 promoter contains three Sp-1/GC binding sites around -50 bp and two NF-kB binding sites at -380 bp and -160 bp from the transcriptional start site of the TLR-5 gene. Sp-1/GC is primarily responsible for the constitutive TLR-5 expression, and may also contribute to NF-kB at -160 bp to induce TLR-5 after atRA stimulation in THP-1 cells. The role of NF-kB in TLR-5 expression was further confirmed by inhibitor pyrrolidine dithiocarbamate (PDTC) experiments, which greatly reduced the TLR-5 transcription by 70-80%. CONCLUSION: atRA induces the expression of the human TLR-5 gene and NF-kB is a critical transcription factor for the atRA-induced expression of TLR-5. Accordingly, it is conceivable that retinoids are required for adequate innate and adaptive immune responses to agents of infectious diseases. atRA and various synthetic retinoids have been used therapeutically in human diseases, such as leukemia and other cancers due to the antiproliferative and apoptosis inducing effects of retinoids. Therefore, 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.
