Opposite effect of angiotensin receptor blockade on CXCL8 production and CXCR1/2 expression of angiotensin II‑treated THP‑1 monocytes

Vogiatzi,Konstantina; Apostolakis,Stavros; Vlata,Zaharenia; Krabovitis,Elias; Spandidos,Demetrios  A.

doi:10.3892/etm.2013.909

Opposite effect of angiotensin receptor blockade on CXCL8 production and CXCR1/2 expression of angiotensin II‑treated THP‑1 monocytes

Authors:
- Konstantina Vogiatzi
- Stavros Apostolakis
- Zaharenia Vlata
- Elias Krabovitis
- Demetrios A. Spandidos
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Affiliations: Laboratory of Clinical Virology, Faculty of Medicine University of Crete, Heraklion 71003, Crete, Greece, Institute of Molecular Biology and Biotechnology, Department of Applied Bioschemistry and Immunology, Heraklion 71003, Crete, Greece
Published online on: January 21, 2013 https://doi.org/10.3892/etm.2013.909
Pages: 987-991

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Abstract

Interleukin‑8 (IL‑8) or CXCL8 is a potent chemotactic factor that is involved in atherogenesis. IL‑8 mediates its pre‑inflammatory effects through interaction with CXCR1 and CXCR2. In the present study, we investigated the effects of angiotensin II (Ang II) on IL‑8 synthesis and CXCR1/CXCR2 expression of THP‑1 monocytes. IL‑8 was measured in the culture medium using ELISA. Expression of chemokine receptors CXCR1 and CXCR2 was evaluated by flow cytometry. Results demonstrated that the addition of Ang II increased IL‑8 production in the THP‑1 monocytes. The Ang II type 1 receptor blocker (ARB) losartan significantly blocked Ang II‑induced IL‑8 production. Notably, losartan blocked LPS‑induced IL‑8 production by THP‑1 monocytes and produced a small but statistically significant reduction of baseline IL‑8 production of naïve THP‑1 cells. Losartan also produced a statistically significant increase of fluorescence intensity of naïve CXCR1‑ and CXCR2‑positive THP‑1 monocytes, probably as a negative feedback effect secondary to IL‑8 downregulation. In conclusion, we demonstrated that Ang II increased IL‑8 production by THP‑1 monocytes. Losartan significantly suppressed the latter effect, suggesting an AT‑1 mediated pathway. Moreover, losartan suppressed the IL‑8 production of naïve THP‑1 monocytes and LPS‑treated THP‑1 monocytes, suggesting a broader spectrum of pleiotropic effects. Extrapolating this in vitro observation to in vivo pathways, we propose Ang II‑induced IL‑8 production by monocytes as another pre‑atherogenic potential of Ang II that can be effectively blocked by the AT1 receptor blockade.

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1.	Apostolakis S, Vogiatzi K, Amanatidou V and Spandidos DA: Interleukin 8 and cardiovascular disease. Cardiovasc Res. 84:353–360. 2009. View Article : Google Scholar
2.	Ryoo SW, Kim DU, Won M, Chung KS, Jang YJ, Oh GT, Park SK, Maeng PJ, Yoo HS and Hoe KL: Native LDL induces interleukin-8 expression via H₂O₂, p38 kinase, and activator protein-1 in human aortic smooth muscle cells. Cardiovasc Res. 62:185–193. 2004. View Article : Google Scholar : PubMed/NCBI
3.	Dje N’Guessan P, Riediger F, Vardarova K, Scharf S, Eitel J, Opitz B, Slevogt H, Weichert W, Hocke AC, Schmeck B, Suttorp N and Hippenstiel S: Statins control oxidized LDL-mediated histone modifications and gene expression in cultured human endothelial cells. Arterioscler Thromb Vasc Biol. 29:380–386. 2009.PubMed/NCBI
4.	Dandona P, Dhindsa S, Ghanim H and Chaudhuri A: Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade. J Hum Hypertens. 21:20–27. 2007. View Article : Google Scholar : PubMed/NCBI
5.	Apostolakis S, Vlata Z, Vogiatzi K, Krambovitis E and Spandidos DA: Angiotensin II up-regulates CX3CR1 expression in THP-1 monocytes: impact on vascular inflammation and atherogenesis. J Thromb Thrombolysis. 29:443–448. 2010. View Article : Google Scholar : PubMed/NCBI
6.	Ferrario CM and Strawn WB: Role of the renin-angiotensin aldosterone system and proinflammatory mediators in cardiovascular disease. Am J Cardiol. 98:121–128. 2006. View Article : Google Scholar : PubMed/NCBI
7.	Apostolakis S, Krambovitis E, Vlata Z, Kochiadakis GE, Baritaki S and Spandidos DA: CX3CR1 receptor is up-regulated in monocytes of coronary artery diseased patients: impact of pre-inflammatory stimuli and renin-angiotensin system modulators. Thromb Res. 121:387–395. 2007. View Article : Google Scholar
8.	Koh KK, Ahn JY, Han SH, Kim DS, Jin DK, Kim HS, Shin MS, Ahn TH, Choi IS and Shin EK: Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients. J Am Coll Cardiol. 42:905–910. 2003. View Article : Google Scholar : PubMed/NCBI
9.	Sierra C and de la Sierra A: Antihypertensive, cardiovascular, and pleiotropic effects of angiotensin-receptor blockers. Curr Opin Nephrol Hypertens. 14:435–441. 2005. View Article : Google Scholar : PubMed/NCBI
10.	Devlin RB, Frampton ML and Ghio AJ: In vitro studies: what is their role in toxicology? Exp Toxicol Pathol. 57(Suppl 1): 183–188. 2005. View Article : Google Scholar : PubMed/NCBI
11.	Tsuchiya S, Yamabe M, Yamaguchi Y, Kobayashi Y, Konno T and Tada K: Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer. 26:171–176. 1980. View Article : Google Scholar : PubMed/NCBI
12.	Chen M, Li Y, Yang T, Wang Y, Bai Y and Xie X: ADMA induces monocyte adhesion via activation of chemokine receptors in cultured THP-1 cells. Cytokine. 43:149–159. 2008. View Article : Google Scholar : PubMed/NCBI
13.	Schmeisser A, Soehnlein O, Illmer T, Lorenz HM, Eskafi S, Roerick O, Gabler C, Strasser R, Daniel WG and Garlichs CD: ACE inhibition lowers angiotensin II-induced chemokine expression by reduction of NF-kappaB activity and AT1 receptor expression. Biochem Biophys Res Commun. 325:532–540. 2004. View Article : Google Scholar : PubMed/NCBI
14.	Chishti AD, Dark JH, Kesteven P, Powell H, Snowden C, Shenton BK, Kirby JA and Baudouin SV: Expression of chemokine receptors CXCR1 and CXCR2 during cardiopulmonary bypass. J Thorac Cardiovasc Surg. 122:1162–1166. 2001. View Article : Google Scholar : PubMed/NCBI
15.	Gessler P, Pfenninger J, Pfammatter JP, Carrel T, Baenziger O and Dahinden C: Plasma levels of interleukin-8 and expression of interleukin-8 receptors on circulating neutrophils and monocytes after cardiopulmonary bypass in children. J Thorac Cardiovasc Surg. 126:718–725. 2003. View Article : Google Scholar : PubMed/NCBI
16.	Browning DD, Diehl WC, Hsu MH, Schraufstatter IU and Ye RD: Autocrine regulation of interleukin-8 production in human monocytes. Am J Physiol Lung Cell Mol Physiol. 279:L1129–L1136. 2000.PubMed/NCBI
17.	Samanta AK, Oppenheim JJ and Matsushima K: Interleukin 8 (monocyte-derived neutrophil chemotactic factor) dynamically regulates its own receptor expression on human neutrophils. J Biol Chem. 265:183–189. 1990.