Carnosol inhibits cell adhesion molecules and chemokine expression by tumor necrosis factor-α in human umbilical vein endothelial cells through the nuclear factor-κB and mitogen-activated protein kinase pathways

Yao,Hui; Chen,Yufeng; Zhang,Longjuan; He,Xiaosheng; He,Xiaowen; Lian,Lei; Wu,Xiaojian; Lan,Ping

doi:10.3892/mmr.2013.1839

Carnosol inhibits cell adhesion molecules and chemokine expression by tumor necrosis factor-α in human umbilical vein endothelial cells through the nuclear factor-κB and mitogen-activated protein kinase pathways

Authors:
- Hui Yao
- Yufeng Chen
- Longjuan Zhang
- Xiaosheng He
- Xiaowen He
- Lei Lian
- Xiaojian Wu
- Ping Lan
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Affiliations: Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangdong Gastrointestinal Hospital, Guangzhou, Guangdong 510655, P.R. China, Laboratory of Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: December 3, 2013 https://doi.org/10.3892/mmr.2013.1839
Pages: 476-480

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Abstract

Inflammatory bowel diseases (IBD) are gastrointestinal disorders associated with chronic inflammatory processes. Carnosol has been demonstrated to possess anti-inflammatory properties. This study examined the suppressive effect of carnosol on the expression of cell adhesion molecules (CAMs) and chemokines in human umbilical vein endothelial cells (HUVECs) and the possible underlying mechanism. The effect of carnosol on CAM and chemokine expression in HUVECs was identified by western blotting and ELISA, respectively. nuclear factor (NF)-κB activation of HUVECs was analyzed using the TransAM NF-κB Family kit. The effect of carnosol on the tumor necrosis factor (TNF)-α-induced activation of the NF-κB and mitogen-activated protein kinase (MAPK) pathways, and was subsequently analyzed using western blotting. Carnosol not only inhibited TNF-α-induced protein expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and E-selectin in HUVECs, but also suppressed interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 expression. In addition, carnosol inhibited the TNF-α-induced phosphorylation of p-65 and IκB-α, as well as the activation of NF-κB. The same result was observed in TNF-α-stimulated phosphorylation of ERK1/2 and p-38. It was demonstrated that carnosol inhibited TNF-α-induced CAM and chemokine expression in HUVECs. The underlying mechanism may be associated with the blocking of the NF-κB and MAPK pathways. These results indicate that carnosol may be a novel therapeutic agent for targeting endothelial cells in IBDs.

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1	Khor B, Gardet A and Xavier RJ: Genetics and pathogenesis of inflammatory bowel disease. Nature. 474:307–317. 2011. View Article : Google Scholar
2	Danese S: Inflammation and the mucosal microcirculation in inflammatory bowel disease: the ebb and flow. Curr Opin Gastroenterol. 23:384–389. 2007. View Article : Google Scholar : PubMed/NCBI
3	Ghosh N, Chaki R and Mandal SC: Inhibition of selective adhesion molecules in treatment of inflammatory bowel disease. Int Rev Immunol. 31:410–427. 2012. View Article : Google Scholar : PubMed/NCBI
4	Cheng Q, McKeown SJ, Santos L, Santiago FS, Khachigian LM, Morand EF and Hickey MJ: Macrophage migration inhibitory factor increases leukocyte-endothelial interactions in human endothelial cells via promotion of expression of adhesion molecules. J Immunol. 185:1238–1247. 2010. View Article : Google Scholar
5	Danese S and Fiocchi C: Etiopathogenesis of inflammatory bowel diseases. World J Gastroenterol. 12:4807–4812. 2006.PubMed/NCBI
6	Ninomiya K, Matsuda H, Shimoda H, Nishida N, Kasajima N, Yoshino T, Morikawa T and Yoshikawa M: Carnosic acid, a new class of lipid absorption inhibitor from sage. Bioorg Med Chem Lett. 14:1943–6. 2004. View Article : Google Scholar : PubMed/NCBI
7	Weckesser S, Engel K, Simon-Haarhaus B, Wittmer A, Pelz K and Schempp CM: Screening of plant extracts for antimicrobial activity against bacteria and yeasts with dermatological relevance. Phytomedicine. 14:508–516. 2007. View Article : Google Scholar : PubMed/NCBI
8	Poeckel D, Greiner C, Verhoff M, et al: Carnosic acid and carnosol potently inhibit human 5-lipoxygenase and suppress pro-inflammatory responses of stimulated human polymorphonuclear leukocytes. Biochem Pharmacol. 76:91–97. 2008. View Article : Google Scholar
9	Kim SJ, Kim JS, Cho HS, Lee HJ, Kim SY, Kim S, Lee SY and Chun HS: Carnosol, a component of rosemary (Rosmarinus officinalis L.) protects nigral dopaminergic neuronal cells. Neuroreport. 17:1729–1733. 2006.PubMed/NCBI
10	Satoh T, Izumi M, Inukai Y, et al: Carnosic acid protects neuronal HT22 cells through activation of the antioxidant-responsive element in free carboxylic acid- and catechol hydroxyl moieties-dependent manners. Neurosci Lett. 434:260–265. 2008. View Article : Google Scholar
11	Johnson JJ, Syed DN, Suh Y, Heren CR, Saleem M, Siddiqui IA and Mukhtar H: Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: implications for chemoprevention. Cancer Prev Res (Phila). 3:1112–1123. 2010. View Article : Google Scholar : PubMed/NCBI
12	Yu YM, Lin CH, Chan HC and Tsai HD: Carnosic acid reduces cytokine-induced adhesion molecules expression and monocyte adhesion to endothelial cells. Eur J Nutr. 48:101–106. 2009. View Article : Google Scholar : PubMed/NCBI
13	Lian KC, Chuang JJ, Hsieh CW, Wung BS, Huang GD, Jian TY and Sun YW: Dual mechanisms of NF-kappaB inhibition in carnosol-treated endothelial cells. Toxicol Appl Pharmacol. 245:21–35. 2010. View Article : Google Scholar : PubMed/NCBI
14	Adachi D, Oda T, Yagasaki H, Nakasato K, Taniguchi T, D’Andrea AD, Asano S and Yamashita T: Heterogeneous activation of the Fanconi anemia pathway by patient-derived FANCA mutants. Hum Mol Genet. 11:3125–3134. 2002. View Article : Google Scholar : PubMed/NCBI
15	Scaldaferri F, Sans M, Vetrano S, et al: Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease. J Clin Invest. 117:1951–1960. 2007. View Article : Google Scholar : PubMed/NCBI
16	Vestweber D: Adhesion and signaling molecules controlling the transmigration of leukocytes through endothelium. Immunol Rev. 218:178–196. 2007. View Article : Google Scholar : PubMed/NCBI
17	Ley K, Laudanna C, Cybulsky MI and Nourshargh S: Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 7:678–689. 2007. View Article : Google Scholar : PubMed/NCBI
18	Baggiolini M and Loetscher P: Chemokines in inflammation and immunity. Immunol Today. 21:418–420. 2000. View Article : Google Scholar : PubMed/NCBI
19	Lehmann JC, Jablonski-Westrich D, Haubold U, Gutierrez-Ramos JC, Springer T and Hamann A: Overlapping and selective roles of endothelial intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 in lymphocyte trafficking. J Immunol. 171:2588–2593. 2003. View Article : Google Scholar : PubMed/NCBI
20	Reiss Y and Engelhardt B: T cell interaction with ICAM-1-deficient endothelium in vitro: transendothelial migration of different T cell populations is mediated by endothelial ICAM-1 and ICAM-2. Int Immunol. 11:1527–1539. 1999.PubMed/NCBI
21	Funakoshi T, Yamashita K, Ichikawa N, et al: A novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates inflammatory colonic injury in mice. J Crohns Colitis. 6:215–225. 2002. View Article : Google Scholar
22	Andresen L, Jørgensen VL, Perner A, Hansen A, Eugen-Olsen J and Rask-Madsen J: Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis. Gut. 54:503–509. 2005. View Article : Google Scholar : PubMed/NCBI
23	Viatour P, Merville MP, Bours V and Chariot A: Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem Sci. 30:43–52. 2005. View Article : Google Scholar : PubMed/NCBI
24	Mitsuyama K, Suzuki A, Tomiyasu N, et al: Pro-inflammatory signaling by Jun-N-terminal kinase in inflammatory bowel disease. Int J Mol Med. 17:449–455. 2006.PubMed/NCBI
25	Scaldaferri F, Sans M, Vetrano S, et al: The role of MAPK in governing lymphocyte adhesion to and migration across the microvasculature in inflammatory bowel disease. Eur J Immunol. 39:290–300. 2009. View Article : Google Scholar : PubMed/NCBI
26	Hollenbach E, Neumann M, Vieth M, Roessner A, Malfertheiner P and Naumann M: Inhibition of p38 MAP kinase- and RICK/NF-kappaB-signaling suppresses inflammatory bowel disease. FASEB J. 18:1550–1552. 2004.PubMed/NCBI
27	Ghosh S and Panaccione R: Anti-adhesion molecule therapy for inflammatory bowel disease. Therap Adv Gastroenterol. 3:239–258. 2010. View Article : Google Scholar : PubMed/NCBI
28	Zhang W, Yang AL, Liao J, et al: Soluble epoxide hydrolase gene deficiency or inhibition attenuates chronic active inflammatory bowel disease in IL-10(−/−) mice. Dig Dis Sci. 57:2580–2591. 2012.