Browse > Article
http://dx.doi.org/10.15616/BSL.2020.26.4.256

All-trans Retinoic Acid Induces Expression and Secretion of Carboxypeptidase D in THP-1 Cells  

Nguyen, Hang Thi Thu (Department of Life Science, Gachon University)
Kim, Jae Young (Department of Life Science, Gachon University)
Publication Information
Biomedical Science Letters / v.26, no.4, 2020 , pp. 256-266 More about this Journal
Abstract
Carboxypeptidase D (CPD) is a zinc-dependent protease, which is highly expressed in macrophages, and is thought to participate in inflammatory processes. In the present study, we investigated the possible regulatory effect of all-trans retinoic acid (ATRA), which is an active form of vitamin A and plays a critical regulatory role in both the innate and adaptive immunity, on CPD expression and secretion in human monocytic THP-1 cells. CPD mRNA expression first increased, from a concentration as low as 10 nM ATRA to a maximum level of expression, at 1 μM. ATRA enhanced intracellular CPD expression in a time- and concentration-dependent manner but did not affect cell surface CPD expression. Interestingly, 9-cis-RA did not affect CPD expression. Additionally, an experiment with RAR/RXR selective agonist or antagonists demonstrated that ATRA-induced enhancement of CPD expression was RAR/RXR dependent. ATRA also enhanced CPD secretion from THP-1 cells; however, this enhancement was RAR/RXR-independent. The anti-inflammatory agent dexamethasone reversed ATRA-induced enhancement of CPD expression and secretion. Our results suggest ATRA exerts regulatory effects on expression and secretion of CPD in human monocytes, and ATRA-induced CPD secretion may be associated with inflammatory response.
Keywords
All-trans retinoic acid; Carboxypeptidase D; THP-1; Monocytes; Vitamin A; Secretion; Inflammation;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Varlamov O, Eng FJ, Novikova EG, et al. Localization of metallocarboxypeptidase D in AtT-20 cells. Potential role in prohormone processing. J Biol Chem. 1999. 274: 14759-14767.   DOI
2 Varlamov O, Fricker LD. Intracellular trafficking of metallocarboxypeptidase D in AtT-20 cells: localization to the transGolgi network and recycling from the cell surface. J Cell Sci. 1998. 111: 877-885.   DOI
3 Vu HT, Hoang TX, Kim JY. All-trans retinoic acid enhances matrix metalloproteinase 2 expression and secretion in human myeloid leukemia THP-1 cells. Biomed Res Int. 2018. 2018: article ID 5971080.
4 Wang X, Allen C, Ballow M. Retinoic acid enhances the production of IL-10 while reducing the synthesis of IL-12 and TNF-α from LPS-stimulated monocytes/macrophages. J Clin Immunol. 2007. 27: 193-200.   DOI
5 Hoang TX, Jung JH, Kim JY. All-trans retinoic acid enhances bacterial flagellin-stimulated proinflammatory responses in human monocyte THP-1 cells by upregulating CD14. BioMed Res Int. 2019. 2019: article ID 8059312.
6 Hoff NP, Degrandi D, Hengge U, et al. Carboxypeptidase D: a novel TGF-beta target gene dysregulated in patients with lupus erythematosus. J Clin Immunol. 2007. 27: 568-579.   DOI
7 Kalinina E, Varlamov O, Fricker LD. Analysis of the carboxypeptidase D cytoplasmic domain: Implications in intracellular trafficking. J Cell Biochem. 2002. 85: 101-111.   DOI
8 Huber-Lang MS, Sarma JV, McGuire SR, et al. Structure-function relationships of human C5a and C5aR. J Immunol. 2003. 170: 6115-6124.   DOI
9 Iwata M, Hirakiyama A, Eshima Y, et al. Retinoic acid imprints gut-homing specificity on T cells. Immunity. 2004. 21: 527-538.   DOI
10 Jeremic A, Kelly M, Cho JA, et al. Calcium drives fusion of SNARE-apposed bilayers. Cell Biol Int. 2004. 28: 19-31.   DOI
11 Kang BY, Chung SW, Kim SH, et al. Retinoid-mediated inhibition of interleukin-12 production in mouse macrophages suppresses Th1 cytokine profile in CD4(+) T cells. Brit J Pharmacol. 2000. 130: 581-586.   DOI
12 Abdelmagid SA, Too CK. Prolactin and estrogen up-regulate carboxypeptidase-d to promote nitric oxide production and survival of mcf-7 breast cancer cells. Endocrinology. 2008. 149: 4821-4828.   DOI
13 Bastien J, Rochette-Egly C. Nuclear retinoid receptors and the transcription of retinoid-target genes. Gene. 2004. 328: 1-16.   DOI
14 Bhoola KD, Figueroa CD, Worthy K. Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev. 1992. 44: 1-80.
15 Gao ZY, Xu G, Stwora-Wojczyk MM, et al. Retinoic acid induction of calcium channel expression in human NT2N neurons. Biochem Biophys Res Commun. 1998. 247: 407-413.   DOI
16 Brooks SC 3rd, Kazmer S, Levin AA, et al. Myeloid differentiation and retinoblastoma phosphorylation changes in HL-60 cells induced by retinoic acid receptor- and retinoid X receptor-selective retinoic acid analogs. Blood. 1996. 87: 227-237.
17 deBlois D, Bouthillier J, Marceau F. Pulse exposure to protein synthesis inhibitors enhances vascular responses to des-Arg9-bradykinin: possible role of interleukin-1. Br J Pharmacol. 1991. 103: 1057-1066.   DOI
18 DePaolo RW, Abadie V, Tang F, et al. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature. 2011. 471: 220-224.   DOI
19 Elias KM, Laurence A, Davidson TS. Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood. 2008. 111: 1013-1020.   DOI
20 Eriksen AB, Berge T, Gustavsen MW, et al. Retinoic acid enhances the levels of IL-10 in TLR-stimulated B cells from patients with relapsing-remitting multiple sclerosis. J Neuroimmunol. 2015. 278: 11-18.   DOI
21 Garcia-Pardo J, Tanco S, Diaz L, et al. Substrate specificity of human metallocarboxypeptidase D: Comparison of the two active carboxypeptidase domains. PLoS One. 2017. 12: e0187778.   DOI
22 Botling J, Castro DS, Oberg F, et al. Retinoic acid receptor/retinoid X receptor heterodimers can be activated through both subunits providing a basis for synergistic transactivation and cellular differentiation. J Biol Chem. 1997. 272: 9443-9449.   DOI
23 Gundra UM, Girgis NM, Gonzalez MA, et al. Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation. Nature Immunology. 2017. 18: 642-653.   DOI
24 Lu ZX, Fok KF, Erickson BW, et al. Conformational analysis of COOH-terminal segments of human C3a. Evidence of ordered conformation in an active 21-residue peptide. J Biol Chem. 1984. 259: 7367-7370.   DOI
25 Kim CH. Control of innate and adaptive lymphocytes by the RAR-retinoic acid axis. Immune Netw. 2018. 18: e1.   DOI
26 Klebanoff CA, Spencer SP, Torabi-Parizi P, et al. Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells. J Exp Med. 2013. 210: 1961-1976.   DOI
27 Koirala S, Thomas LN, Too CK. Prolactin/Stat5 and androgen R1881 coactivate carboxypeptidase-D gene in breast cancer cells. Mol Endocrinol. 2014. 28: 331-343.   DOI
28 Manoury B. Proteases: essential actors in processing antigens and intracellular toll-like receptors. Front Immunol. 2013. 4: 299.   DOI
29 Marshall NC, Finlay BB, Overall CM. Sharpening host defenses during infection: proteases cut to the chase. Mol Cell Proteomics. 2017. 16: S161-S171.   DOI
30 Mehta K, McQueen T, Tucker S, et al. Inhibition by all-transretinoic acid of tumor necrosis factor and nitric oxide production by peritoneal macrophages. J Leuk Biol. 1994. 55: 336-342.   DOI
31 Hadkar V, Sangsree S, Vogel SM, et al. Carboxypeptidase-mediated enhancement of nitric oxide production in rat lungs and microvascular endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2004. 287: L35-L45.
32 Mielke LA, Jones SA, Raverdeau M, et al. Retinoic acid expression associates with enhanced IL-22 production by gammadelta T cells and innate lymphoid cells and attenuation of intestinal inflammation. J Exp Med. 2013. 210: 1117-1124.   DOI
33 Scheffel F, Heine G, Henz BM, et al. Retinoic acid inhibits CD40 plus IL-4 mediated IgE production through alterations of sCD23, sCD54 and IL-6 production. Inflamm Res. 2005. 54: 113-118.   DOI
34 Naffah-Mazzacoratti Mda G, Gouveia TL, Simoes PS, et al. What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders? World J Biol Chem. 2014. 5: 130-140.   DOI
35 Hadkar V, Skidgel RA. Carboxypeptidase D is up-regulated in raw 264.7 macrophages and stimulates nitric oxide synthesis by cells in arginine-free medium. Mol Pharmacol. 2001. 59: 1324-1332.   DOI
36 Hall, JA, Cannons JL, Grainger JR, et al. Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha. Immunity. 2011. 34: 435-447.   DOI
37 Ho VW, Hofs E, Elisia I, et al. All trans retinoic acid, transforming growth factor β and prostaglandin E2 in mouse plasma synergize with basophil-secreted interleukin-4 to M2 polarize murine macrophages. PLoS One. 2016. 11: article e0168072.
38 Parks WC, Wilson CL, Lopez-Boado YS. Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol. 2004. 4: 617-629.   DOI
39 Pasupuleti M, Walse B, Nordahl EA, et al. Preservation of antimicrobial properties of complement peptide C3a, from invertebrates to humans. J Biol Chem. 2007. 282: 2520-2528.   DOI
40 Reznik SE, Fricker LD. Carboxypeptidases from A to Z: implications in embryonic development and Wnt binding. Cell Mol Life Sci. 2001. 58: 1790-1804.   DOI
41 Sim RB, Laich A. Serine proteases of the complement system. Biochem Soc Trans. 2000. 28: 545-550.   DOI
42 Skidgel RA, Erdos EG. Cellular carboxypeptidases. Immunol Rev. 1998. 161: 129-141.   DOI
43 Steer JH, Kroeger KM, Abraham LJ, et al. Glucocorticoids suppress tumor necrosis factor-alpha expression by human monocytic THP-1 cells by suppressing transactivation through adjacent NF-kappa B and c-Jun-activating transcription factor-2 binding sites in the promoter. J Biol Chem. 2000. 275: 18432-18440.   DOI
44 Skidgel RA. Basic carboxypeptidases: regulators of peptide hormone activity. Trends Pharmacol Sci. 1988. 9: 299-304.   DOI
45 Niederreither K, Dolle P. Retinoic acid in development: towards an integrated view. Nat Rev Genet. 2008. 9: 541-553.   DOI
46 Skidgel RA. Structure and function of mammalian zinc carboxypeptidases. In zinc metalloproteases in health and disease. CRC Press. 1996. 261-304.
47 Stephan AH, Barres BA, Stevens B. The complement system: an unexpected role in synaptic pruning during development and disease. Annu Rev Neurosci. 2012. 35: 369-389.   DOI
48 Tsai MJ, O'Malley BW. Molecular mechanisms of action of steroid /thyroid receptor superfamily members. Annu Rev Biochem. 1994. 63: 451-486.   DOI
49 Thomas LN, Morehouse TJ, Too CK. Testosterone and prolactin increase carboxypeptidase-D and nitric oxide levels to promote survival of prostate cancer cells. Prostate. 2012. 72: 450-460.   DOI
50 Timblin B, Rehli M, Skidgel RA. Structural characterization of the human carboxypeptidase D gene and its promoter. Int Immunopharmacol. 2002. 2: 1907-1917.   DOI