Effects of all-trans retinoic acid on Th1- and Th2-related chemokines production in monocytes.
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.
Tsai
Yu-Chien
YC
Department of Pediatrics, Chi-Mei Medical Center, Tainan, Taiwan, Republic of China.
Chang
Hui-Wen
HW
Chang
Tai-Tsung
TT
Lee
Min-Sheng
MS
Chu
Yu-Te
YT
Hung
Chih-Hsing
CH
D001205:Ascorbic Acid / Q000494:pharmacology; D002460:Cell Line; D054422:Chemokine CCL22 / Q000235:genetics / Q000378:metabolism*; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D010766:Phosphorylation; D011070:Poly I-C / Q000494:pharmacology; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
C515482:CCL22 protein, human; C114753:CXCL10 protein, human; D054422:Chemokine CCL22; D054357:Chemokine CXCL10; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D014212:Tretinoin; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D011070:Poly I-C; D001205:Ascorbic Acid