The Effect of Artemisinin on Inflammation-Associated Lymphangiogenesis in Experimental Acute Colitis
Abstract
:1. Introduction
2. Results
2.1. Art Reduces Inflammatory Lymphangiogenesis in Mice with DSS-Induced Colitis
2.2. Art Attenuates the Symptoms of Colitis, Improves Tissue Histology, and Relieves Inflammatory Edema in Mice with Colitis
2.3. Art Decreases the Infiltration of Immunomodulatory Cells during Colitis
2.4. Art Reduces the Expression of Proinflammatory Cytokines in Mice with DSS-Induced Colitis
2.5. Art Improves Lymph Flow in DSS-Induced Colitis
3. Discussion
4. Materials and Methods
4.1. Animal Model
4.2. Assessment of Disease Severity
4.3. Histopathological Analysis
4.4. Immunofluorescence Analysis
4.5. Immunohistochemistry Analysis
4.6. Quantitative Real-Time PCR
4.7. Enzyme-Linked Immunosorbent Assay (ELISA)
4.8. Evans Blue Dye Assay
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
IBD | inflammatory bowel disease |
DSS | dextran sulfate sodium |
PECAM-1 | platelet endothelial cell adhesion molecule-1 |
LYVE-1 | lymphatic vessel endothelial hyaluronan receptor-1 |
DAI | disease activity index |
LVD | lymphatic vessel density |
VEGF | vascular endothelial growth factor |
IL-1 β | interleukin-1β |
IFN-γ | Interferon-γ |
TNF-α | Tumor necrosis factor-α |
References
- Gerova, V.A.; Stoynov, S.G.; Katsarov, D.S.; Svinarov, D.A. Increased intestinal permeability in inflammatory bowel diseases assessed by iohexol test. World J. Gastroenterol. 2011, 17, 2211–2215. [Google Scholar] [CrossRef] [PubMed]
- Sato, H.; Higashiyama, M.H.; Hozumi, H.; Sato, S.; Furuhashi, H.; Takajo, T.; Maruta, K.; Yasytaje, Y.; Narimatsu, K.; Yoshikawa, K.; et al. Platelet interaction with lymphatics aggravates intestinal inflammation by suppressing lymphangiogenesis. Am. J. Physiol. Gastrointest. Liver Physiol. 2016, 311, G276–G285. [Google Scholar] [CrossRef] [Green Version]
- Tan, K.W.; Chong, S.Z.; Angeli, V. Inflammatory lymphangiogenesis: Cellular mediators and functional implications. Angiogenesis 2014, 17, 373–381. [Google Scholar] [CrossRef]
- Kim, H.; Kataru, R.P.; Koh, G.Y. Inflammation-associated lymphangiogenesis: A double-edged sword? J. Clin. Investig. 2014, 124, 936–942. [Google Scholar] [CrossRef] [PubMed]
- Danese, S.; Sans, M.; Motte, C.; Craziani, C.; West, G.; Phillips, M.H.; Pola, R.; Rutella, S.; Willis, J.; Gasbarrini, A.; et al. Angiogenesis as a novel component of inflammatory bowel disease pathogenesis. Gastroenterology 2006, 130, 2060–2073. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jeon, E.J.; Davaatseren, M.; Hwang, J.T.; Park, J.H.; Hur, H.J.; Lee, A.S.; Sung, M.J. Effect of oral administration of 3,3’-diindolylmethane on dextran sodium sulfate-induced acute colitis in mice. J. Agric. Food Chem. 2016, 64, 7702–7709. [Google Scholar] [CrossRef] [PubMed]
- Lee, A.S.; Sung, M.J.; Kim, W.; Jung, Y.J. COMP-angiopoietin-1 ameliorates inflammation-induced lymphangiogenesis in dextran sulfate sodium (DSS)-induced colitis model. J. Mol. Med. 2018, 96, 459–467. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- D’Alessio, S.; Tacconi, C.; Fiocchi, C.; Danese, S. Advances in therapeutic interventions targeting the vascular and lymphatic endothelium in inflammatory bowel disease. Curr. Opin. Gastroenterol. 2013, 29, 608–613. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.L.; Zhao, J.; Qin, L. Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis. Braz. J. Med. Biol. Res. 2016, 49, e4738. [Google Scholar] [CrossRef] [Green Version]
- D’Alessio, S.; Correale, C.; Tacconi, C.; Gandelli, A.; Pietrogrande, G.; Vetrano, S.; Genua, M.; Arena, V.; Spinelli, A.; Peyrin-Biroulet, L.; et al. VEGF-C-dependent stimulation of lymphatic function ameliorates experimental inflammatory bowel disease. J. Clin. Investig. 2014, 124, 3863–3878. [Google Scholar] [CrossRef] [Green Version]
- Jurisic, G.; Sundberg, J.P.; Detmar, M. Blockade of VEGF receptor-3 aggravates inflammatory bowel disease and lymphatic vessel enlargement. Inflamm. Bowel Dis. 2013, 19, 1983–1989. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shi, C.; Li, H.; Yang, Y. Anti-inflammatory and immunoregulatory functions of artemisinin and its derivatives. Mediators Inflamm. 2015, 2015, 435713. [Google Scholar] [CrossRef] [Green Version]
- Meshnick, S.M.; Taylor, T.E.; Kamchonwongpaisan, S. Artemisinin and the antimalarial endoperoxides: From herbal remedy to targeted chemotherapy. Microbiol. Rev. 1996, 60, 301–315. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aldieri, E.; Atragene, D.; Bergandi, L.; Riganti, C.; Costamagna, C.; Bosia, A.; Ghigo, D. Artemisinin inhibits inducible nitric oxide synthase and nuclear factor NF-kB activation. FEBS Lett. 2003, 552, 141–144. [Google Scholar] [CrossRef] [Green Version]
- Wang, K.S.; Li, J.; Wang, Z.; Mi, C.; Ma, J.; Piao, L.X.; Xu, G.H.; Li, X.; Jin, X. Artemisinin inhibits inflammatory response via regulating NF-kB and MAPK signaling pathways. Immunopharmacol. Immunotoxicol. 2017, 39, 28–36. [Google Scholar] [CrossRef]
- Das, A. Anticancer effect of antimalarial artemisinin compounds. Ann. Med. Health Sci. Res. 2015, 5, 93–102. [Google Scholar] [CrossRef]
- Cheng, R.; Li, C.; Li, C.; Wei, L.; Li, L.; Zhang, Y.; Yao, Y.; Gu, X.; Cai, W.; Yang, Z.; et al. The artemisinin derivative artesunate inhibits corneal neovascularization by inducing ROS-dependent apoptosis in vascular endothelial cells. Investig. Ophthalmol. Vis. Sci. 2013, 54, 3400–3409. [Google Scholar] [CrossRef] [Green Version]
- Hu, D.; Wang, Y.; Chenet, Z.; Ma, Z.; You, Q.; Zhang, X.; Zhou, T.; Xiao, Y.; Liang, Q.; Tan, H.; et al. Artemisinin protects against dextran sulfate-sodium-induced inflammatory bowel disease, which is associated with activation of the pregnane X receptor. Eur. J. Pharmacol. 2014, 738, 273–284. [Google Scholar] [CrossRef] [PubMed]
- Pousa, D.I.; Jimenez, J.M.; Mora, X.S.; Abereu, M.T.; Otero, R.M.; Gisbert, J.P. Analysis of soluble angiogenic factors in Crohn’s disease: A preliminary study. Análisis de los factores angiogénicos solubles en la enfermedad de crohn: Un estudio preliminar. Gastroenterol. Hepatol. 2007, 30, 518–524. [Google Scholar] [CrossRef]
- Rodriguez-Canales, M.; Martinez-Galero, E.; Nava-Torres, A.D.; Sanchez-Torres, L.E.; Garduno-Siciliano, L.; Canales-Martinez, M.M.; Terrazas, L.I.; Rodriguez-Monroy, M.A. Anti-Inflammatory and antioxidant activities of the methanolic extract of Cyrtocarpa procera bark reduces the severity of ulcerative colitis in a chemically induced colitis model. Mediators Inflamm. 2020, 2020, 5062506. [Google Scholar] [CrossRef]
- Kruiningen, H.J.V.; Hayes, A.W.; Colombel, J. Granulomas obstruct lymphatics in all layers of the intestine in Crohn’s disease. APMIS 2014, 122, 1125–1129. [Google Scholar] [CrossRef] [PubMed]
- Hatoum, O.A.; Heidemann, J.; Binion, D.G. The intestinal microvasculature as a therapeutic target in inflammatory bowel disease. Ann. N. Y. Acad. Sci. 2006, 1072, 78–97. [Google Scholar] [CrossRef] [PubMed]
- Pousa, I.D.; Mate, J.; Gisbert, J.P. Angiogenesis in inflammatory bowel disease. Eur. J. Clin. Investig. 2008, 38, 73–81. [Google Scholar] [CrossRef] [PubMed]
- Rugtveit, J.; Brandtzaeg, P.; Halstensen, T.S.; Fausa, O.; Scott, F. Increased macrophage subset in inflammatory bowel disease: Apparent recruitment from peripheral blood monocytes. Gut 1994, 35, 669–674. [Google Scholar] [CrossRef] [Green Version]
- Kaiserling, E.; Krober, S.; Geleff, S. Lymphatic vessels in the colonic mucosa in ulcerative colitis. Lymphology 2003, 36, 52–61. [Google Scholar]
- Griga, T.; Tromm, A.; Spranger, J.; May, B. Increased serum levels of vascular endothelial growth factor in patients with inflammatory bowel disease. Scand. J. Gastroenterol. 1998, 33, 504–508. [Google Scholar] [CrossRef]
- Azzam, N. Angiogenesis and inflammatory bowel disease. Saudi J. Gastroenterol. 2007, 13, 37–38. [Google Scholar] [CrossRef]
- Baluk, P.; Tammela, T.; Ator, E.; Lyubynska, N.; Achen, M.G.; Hichlin, D.J.; Jeltsch, M.; Petrova, T.V.; Pytowski, B.; Stacher, S.A.; et al. Pathogenesis of persistent lymphatic vessel hyperplasia in chronic airway inflammation. J. Clin. Investig. 2005, 115, 247–257. [Google Scholar] [CrossRef] [Green Version]
- Davaatseren, M.; Hwang, J.T.; Park, J.H.; Kim, M.S.; Wang, S.; Sung, M.J. Allyl isothiocyanate ameliorates angiogenesis and inflammation in dextran sulfate sodium-induced acute colitis. PLoS ONE 2014, 9, e102975. [Google Scholar] [CrossRef]
- Davaatseren, M.; Hwang, J.T.; Park, J.H.; Kim, M.S.; Wang, S.; Sung, M.J. Poly-gamma-glutamic acid attenuates angiogenesis and inflammation in experimental colitis. Mediators Inflamm. 2013, 2013, 982383. [Google Scholar] [CrossRef] [Green Version]
- Kim, D.H.; Jung, Y.J.; Lee, A.S.; Lee, S.; Kang, K.P.; Lee, T.H.; Lee, S.Y.; Jang, K.Y.; Moon, W.S.; Choi, K.H.; et al. COMP-angiopoietin-1 decreases lipopolysaccharide-induced acute kidney injury. Kidney. Int. 2009, 76, 1180–1191. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Radu, M.; Chernoff, J. An in vivo assay to test blood vessel permeability. J. Vis. Exp. 2013, 2013, e50062. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lee, A.S.; Hur, H.J.; Sung, M.J. The Effect of Artemisinin on Inflammation-Associated Lymphangiogenesis in Experimental Acute Colitis. Int. J. Mol. Sci. 2020, 21, 8068. https://doi.org/10.3390/ijms21218068
Lee AS, Hur HJ, Sung MJ. The Effect of Artemisinin on Inflammation-Associated Lymphangiogenesis in Experimental Acute Colitis. International Journal of Molecular Sciences. 2020; 21(21):8068. https://doi.org/10.3390/ijms21218068
Chicago/Turabian StyleLee, Ae Sin, Haeng Jeon Hur, and Mi Jeong Sung. 2020. "The Effect of Artemisinin on Inflammation-Associated Lymphangiogenesis in Experimental Acute Colitis" International Journal of Molecular Sciences 21, no. 21: 8068. https://doi.org/10.3390/ijms21218068