Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Inflammation Research
Published in: Inflammation Research 6/2010

01-06-2010 | Original Research Paper

Geniposide inhibits interleukin-6 and interleukin-8 production in lipopolysaccharide-induced human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways

Authors: Hong-Tao Liu, Jun-Lin He, Wen-Ming Li, Zhu Yang, Ying-Xiong Wang, Juan Yin, Yu-Guang Du, Chao Yu

Published in: Inflammation Research | Issue 6/2010

Login to get access

Abstract

Objective

The aim of this study was to investigate the inhibitory effect of geniposide on lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and interleukin-8 (IL-8) production in human umbilical vein endothelial cells (HUVECs).

Materials and methods

Primary HUVECs were used. The mRNA/protein levels of IL-6 and IL-8 was determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). LPS-induced HUVEC migration and adhesion of monocytes to HUVECs were studied by monolayer wound healing experiments and monocytic cell adhesion assay, respectively. Expression of nuclear factor κB (NF-κB), inhibitory factor κB-α (IκB-α), p38 mitogen-activated protein kinase (MAPK) and ERK1/2 were determined by Western blot analysis.

Results

Geniposide effectively inhibited LPS-induced expression of IL-6 and IL-8 in HUVECs at the transcription and translation levels. Additionally, geniposide suppressed LPS-induced HUVEC migration and U937 monocyte adhesion to HUVECs. Signal transduction studies indicate that geniposide blocked the activation of NF-κB, degradation of IκB-α, and phosphorylation of p38 MAPK and ERK1/2 in HUVECs challenged by LPS.

Conclusion

The results show that geniposide can inhibit LPS-induced IL-6 and IL-8 production in HUVECs by blocking p38 MAPK and ERK1/2 signaling pathways.
Literature
1.
Tuo QH, Wang C, Yan FX, Liao DF. MAPK pathway mediates the protective effects of onychin on oxidative stress-induced apoptosis in ECV304 endothelial cells. Life Sci. 2004;76:487–97.CrossRefPubMed
2.
Altman R, Motton DD, Kota RS, Rutledge JC. Inhibition of vascular inflammation by dehydroepiandrosterone sulfate in human aortic endothelial cells: roles of PPARalpha and NF-kappaB. Vascul Pharmacol. 2008;48:76–84.CrossRefPubMed
3.
Li HL, He Y, Zhang JJ, Sun SH, Sun BG. Lipopolysaccharide regulates toll-like receptor 4 expression in human aortic smooth muscle cells. Cell Biol Int. 2007;31:831–5.CrossRefPubMed
4.
Anand AR, Cucchiarini M, Terwilliger EF, Ganju RK. The tyrosine kinase Pyk2 mediates lipopolysaccharide-induced IL-8 expression in human endothelial cells. J Immunol. 2008;180:5636–44.PubMed
5.
Weglarz L, Dzierzewicz Z, Skop B, Orchel A, Parfiniewicz B, Wiśniowska B, et al. Desulfovibrio desulfuricans lipopolysaccharides induce endothelial cell IL-6 and IL-8 secretion and E-selectin and VCAM-1 expression. Cell Mol Biol Lett. 2003;8:991–1003.PubMed
6.
Hashimoto S, Gon Y, Matsumoto K, Maruoka S, Takeshita I, Hayashi S, et al. Selective inhibitor of p38 mitogen-activated protein kinase inhibits lipopolysaccharide-induced interleukin-8 expression in human pulmonary vascular endothelial cells. J Pharmacol Exp Ther. 2000;293:370–5.PubMed
7.
Mantovani A, Bussolino F, Introna M. Cytokine regulation of endothelial cell function: from molecular level to the bedside. Immunol Today. 1997;18:231–40.CrossRefPubMed
8.
Chen QC, Zhang WY, Kim H, Lee IS, Ding Y, Youn UJ et al. Effects of gardeniae fructus extract and geniposide on promoting ligament cell proliferation and collagen synthesis. Phytother Res (in press) 2009. doi: 10.​1002/​ptr.​2839.
9.
Liu JH, Yin F, Guo LX, Deng XH, Hu YH. Neuroprotection of geniposide against hydrogen peroxide induced PC12 cells injury: involvement of PI3 kinase signal pathway. Acta Pharmacol Sin. 2009;30:159–65.CrossRefPubMed
10.
Liu J, Yin F, Zheng X, Jing J, Hu Y. Geniposide, a novel agonist for GLP-1 receptor, prevents PC12 cells from oxidative damage via MAP kinase pathway. Neurochem Int. 2007;51:361–9.CrossRefPubMed
11.
Wang SW, Lai CY, Wang CJ. Inhibitory effect of geniposide on aflatoxin B1-induced DNA repair synthesis in primary cultured rat hepatocytes. Cancer Lett. 1992;65:133–7.CrossRefPubMed
12.
Peng CH, Huang CN, Hsu SP, Wang CJ. Penta-acetyl geniposide-induced apoptosis involving transcription of NGF/p75 via MAPK-mediated AP-1 activation in C6 glioma cells. Toxicology. 2007;238:130–9.CrossRefPubMed
13.
Liaw J, Chao YC. Effect of in vitro and in vivo aerosolized treatment with geniposide on tracheal permeability in ovalbumin-induced guinea pigs. Eur J Pharmacol. 2001;433:115–21.CrossRefPubMed
14.
Wu SY, Wang GF, Liu ZQ, Rao JJ, Lü L, Xu W, et al. Effect of geniposide, a hypoglycemic glucoside, on hepatic regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin. Acta Pharmacol Sin. 2009;30:202–8.CrossRefPubMed
15.
Suzuki Y, Kondo K, Ikeda Y, Umemura K. Antithrombotic effect of geniposide and genipin in the mouse thrombosis model. Planta Med. 2001;67:807–10.CrossRefPubMed
16.
Koo HJ, Lee S, Shin KH, Kim BC, Lim CJ, Park EH. Geniposide, an anti-angiogenic compound from the fruits of Gardenia jasminoides. Planta Med. 2004;70:467–9.CrossRefPubMed
17.
Lee P, Lee J, Choi SY, Lee SE, Lee S, Son D. Geniposide from Gardenia jasminoides attenuates neuronal cell death in oxygen and glucose deprivation-exposed rat hippocampal slice culture. Biol Pharm Bull. 2006;29:174–6.CrossRefPubMed
18.
Unger RE, Krump-Konvalinkova V, Peters K, Kirkpatrick CJ. In vitro expression of the endothelial phenotype: comparative study of primary isolated cells and cell lines, including the novel cell line HPMEC-ST1.6R. Microvasc Res. 2002;64:384–97.CrossRefPubMed
19.
Shen J, DiCorleto PE. ADP stimulates human endothelial cell migration via P2Y1 nucleotide receptor-mediated mitogen-activated protein kinase pathways. Circ Res. 2008;102:448–56.CrossRefPubMed
20.
Galley HF, Dhillon JK, Paterson RL, Webster NR. Effect of ciprofloxacin on the activation of the transcription factors nuclear factor kappaB, activator protein-1 and nuclear factor-interleukin-6, and interleukin-6 and interleukin-8 mRNA expression in a human endothelial cell line. Clin Sci (Lond). 2000;99:405–10.CrossRef
21.
Ozes ON, Mayo LD, Gustin JA, Pfeffer SR, Pfeffer LM, Donner DB. NF-kappaB activation by tumour necrosis factor requires the Akt serine–threonine kinase. Nature. 1999;401:82–5.CrossRefPubMed
22.
Hippenstiel S, Soeth S, Kellas B, Fuhrmann O, Seybold J, Krüll M, et al. Rho proteins and the p38-MAPK pathway are important mediators for LPS-induced interleukin-8 expression in human endothelial cells. Blood. 2000;95:3044–51.PubMed
23.
24.
Endo S, Inada K, Inoue Y, Kuwata Y, Suzuki M, Yamashita H, et al. Two types of septic shock classified by the plasma levels of cytokines and endotoxin. Circ Shock. 1992;38:264–74.PubMed
25.
Desai TR, Leeper NJ, Hynes KL, Gewertz BL. Interleukin-6 causes endothelial barrier dysfunction via the protein kinase C pathway. J Surg Res. 2002;104:118–23.CrossRefPubMed
26.
Noda A, Kinoshita K, Sakurai A, Matsumoto T, Mugishima H, Tanjoh K. Hyperglycemia and lipopolysaccharide decrease depression effect of interleukin 8 production by hypothermia: an experimental study with endothelial cells. Intensive Care Med. 2008;34:109–15.CrossRefPubMed
27.
Oh GS, Pae HO, Choi BM, Lee HS, Kim IK, Yun YG, et al. Penta-O-galloyl-beta-d-glucose inhibits phorbol myristate acetate-induced interleukin-8 [correction of intereukin-8] gene expression in human monocytic U937 cells through its inactivation of nuclear factor-kappaB. Int Immunopharmacol. 2004;4:377–86.CrossRefPubMed
28.
Kaplanski G, Teysseire N, Farnarier C, Kaplanski S, Lissitzky JC, Durand JM, et al. IL-6 and IL-8 production from cultured human endothelial cells stimulated by infection with Rickettsia conorii via a cell-associated IL-1 alpha-dependent pathway. J Clin Invest. 1995;96:2839–44.CrossRefPubMed
29.
Koo HJ, Lim KH, Jung HJ, Park EH. Anti-inflammatory evaluation of gardenia extract, geniposide and genipin. J Ethnopharmacol. 2006;103:496–500.CrossRefPubMed
30.
Malinda KM, Sidhu GS, Banaudha KK, Gaddipati JP, Maheshwari RK, Goldstein AL, et al. Thymosin alpha 1 stimulates endothelial cell migration, angiogenesis, and wound healing. J Immunol. 1998;160:1001–6.PubMed
31.
Thevenard J, Ramont L, Devy J, Brassart B, Dupont-Deshorgue A, Floquet N et al. The YSNSG cyclopeptide derived from tumstatin inhibits tumor angiogenesis by down-regulating endothelial cell migration. Int J Cancer (in press) 2009. doi:10.​1002/​ijc.​24688.
32.
Liu J, Li X, Yue Y, Li J, He T, He Y. The inhibitory effect of quercetin on IL-6 production by LPS-stimulated neutrophils. Cell Mol Immunol. 2005;2:455–60.PubMed
33.
Sun DI, Nizamutdinova IT, Kim YM, Cai XF, Lee JJ, Kang SS, et al. Bisacurone inhibits adhesion of inflammatory monocytes or cancer cells to endothelial cells through down-regulation of VCAM-1 expression. Int Immunopharmacol. 2008;8:1272–81.CrossRefPubMed
34.
Ponce C, Torres M, Galleguillos C, Sovino H, Boric MA, Fuentes A, et al. Nuclear factor kappaB pathway and interleukin-6 are affected in eutopic endometrium of women with endometriosis. Reproduction. 2009;137:727–37.CrossRefPubMed
35.
Huang HP, Shih YW, Wu CH, Lai PJ, Hung CN, Wang CJ. Inhibitory effect of penta-acetyl geniposide on C6 glioma cells metastasis by inhibiting matrix metalloproteinase-2 expression involved in both the PI3K and ERK signaling pathways. Chem Biol Interact. 2009;181:8–14.CrossRefPubMed
36.
Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002;298:1911–2.CrossRefPubMed
37.
Nizamutdinova IT, Oh HM, Min YN, Park SH, Lee MJ, Kim JS, et al. Paeonol suppresses intercellular adhesion molecule-1 expression in tumor necrosis factor-α-stimulated human umbilical vein endothelial cells by blocking p38, ERK and nuclear factor-κB signaling pathways. Int Immunopharmacol. 2007;7:343–50.CrossRefPubMed
38.
Li XY, He JL, Liu HT, Li WM, Yu C. Tetramethylpyrazine suppresses interleukin-8 expression in LPS-stimulated human umbilical vein endothelial cell by blocking ERK, p38 and nulear factor-kappaB signaling pathways. J Ethnopharmacol. 2009;125:83–9.CrossRefPubMed
Metadata
Title
Geniposide inhibits interleukin-6 and interleukin-8 production in lipopolysaccharide-induced human umbilical vein endothelial cells by blocking p38 and ERK1/2 signaling pathways
Authors
Hong-Tao Liu
Jun-Lin He
Wen-Ming Li
Zhu Yang
Ying-Xiong Wang
Juan Yin
Yu-Guang Du
Chao Yu
Publication date
01-06-2010
Publisher
SP Birkhäuser Verlag Basel
Published in
Inflammation Research / Issue 6/2010
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-009-0118-3

Other articles of this Issue 6/2010

Inflammation Research 6/2010 Go to the issue

Review

Immune depression in musculoskeletal trauma

Original Research Paper

Effect of a matrix metalloproteinase-12 inhibitor, S-1, on allergic airway disease phenotypes in mice

Original Research Paper

Hyaluronan reversed proteoglycan synthesis inhibited by mechanical stress: possible involvement of antioxidant effect

Original Research Paper

Sulforaphane suppresses LPS-induced inflammation in primary rat microglia

Original Research Paper

Extramedullary hematopoiesis is dysregulated in histamine-free histidine decarboxylase knockout (HDC−/−) mice

Original Research Paper

Plasma YKL-40 is elevated in patients with recurrent atrial fibrillation after catheter ablation
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits