Effects of All-Trans Retinoic Acid on Th1- and Th2-Related Chemokines Production in Monocytes

Abstract

Low vitamin C and reduced alpha-carotene intake are associated with increased asthma risk in children. In addition, mean serum vitamin A concentrations are significantly lower in asthmatic children than in controls. All-trans retinoic acid (ATRA) is a derivative of vitamin A. Macrophage-derived chemokine (MDC) is a T helper cell-type 2 (Th2)-related chemokine involved in the recruitment of Th2 cells toward inflammatory sites. On the other hand, Th1-related chemokine, interferon-inducible protein 10 (IP-10)/CXCL10 is also important in allergic inflammation. Both Th1- and Th2-related chemokines play an important role in allergic asthma. To survey whether ATRA and ascorbic acid effect Th1- and Th2-related chemokine expression in monocytes. To test this, THP-1 cells were pre-treated with ATRA or ascorbic acid and stimulated by lipopolysaccharide (LPS) or poly I:C. Supernatants were measured for Th2-related (MDC) and Th1-related (IP-10) chemokine concentrations by ELISA. The effects of ATRA on mitogen-activated protein kinase (MAPK) and NFkb were evaluated with Western blotting. After stimulation, ATRA significantly down-regulated MDC and IP-10 in a dose-dependent manner. Similarly, ascorbic acid reduced the LPS-induced changes in MDC but only with a high dose. However, asorbic acid had no effect on IP-10 changes either induced by LPS or poly I:C. RT-PCR showed ATRA inhibited IP-10 expression through decreasing the level of transcription. Furthermore, ATRA suppressed the expression of LPS-stimulated c-Raf, MKK1/2 and ERK expression of THP-1 cells. In conclusion, ATRA suppressed Th2- and Th1-related chemokines expression in THP-1 cells, at least in part via the c-Raf-MKK1/2-ERK/MAPK pathway.

All- trans -retinoic acid represses chemokine expression in adipocytes and adipose tissue by inhibiting NF-κB signaling

“…Similar inhibition of NF-κB signaling has already been reported in various cell models [39], and in 348 transgenic NF-κB reporter mice [40]. To pursue the identification of the precise molecular mechanisms, we …”

All-trans retinoic acid attenuates airway inflammation by inhibiting Th2 and Th17 response in experimental allergic asthma

“…Previous reports showed that ATRA is the biological active metabolite of vitamin A and has an important immunomodulatory effect by inhibiting Th17 polarization and enhancing Foxp3 expression [14-16]. By using a murine Th2-mediated airway inflammation model, we demonstrated that the administration of ATRA attenuated OVA-induced airway inflammation by decreasing Th2 and Th17 related cytokines and inflammatory cells in the airway and ATRA mediated reduction of Th2 cytokines was via inhibiting GATA-3 expression.…”

“…ATRA and rapamycin can synergistically increase TGF-β-mediated Foxp3 induction in antigen-specific Th2 memory cells when effector cytokines are neutralized. These Foxp3 + T cells converted from Th2 memory cells possess Treg activity and can ameliorate Th2 memory-mediated airway hyperreactivity and eosinophilic inflammation [14-20]. Moreover, ATRA suppresses Th2-related chemokine expression in vitro by down-regulating the expression of interleukin (IL)-5 receptor and inhibiting eosinophil and basophil differentiation [21-23].…”

Differential Effects of Vitamins A and D on the Transcriptional Landscape of Human Monocytes during Infection

“…In addition, pathway analysis underpinned the notion that immune response is the most regulated biological function by both vitamins (Supplementary Table S2). Although the immunomodulatory effect of both vitamins has already been described for single genes in different cell models20212324525354, the dimension of this regulatory function has not been previously reported.…”