P-AKT2/SPK1 (P-SPK1) and P-MEK/P-ERK Cell Signaling Pathways Are Involved in LPS-induced Macrophage Migration

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2019 Jun 21

PMID 31217849

Citations 2

Authors

Yonghong Lei

Yanping Yang

Jieqiong Zhao

Haibo Gao

Ruirui Chen

Baobao Bai

Xiaohui Kang

Yong He

Lu Ding

Ting Wei

Xiaobing Fu

Lianyou Zhao

Xue Li

Affiliations

Soon will be listed here.

Abstract

Macrophage recruitment to the inflammation site is essential for LPS-induced myocarditis, although the underlying mechanism remains elusive. This study was designed to examine the role of the P-AKT2/SPK1 (P-SPK1) and P-MEK/P-ERK signaling cascades in the regulation of macrophage migration and LPS-induced myocarditis. Our data revealed that (1) the P-AKT2/SPK1 (P-SPK1) and P-MEK/P-ERK signaling cascades acted separately in the regulation of macrophage migration; (2) P-AKT2/SPK1 (P-SPK1) played a relatively important role compared to P-MEK/P-ERK cell signaling in LPS-induced macrophage migration; (3) atorvastatin (ATV) inhibited macrophage migration by inhibiting P-AKT2/SPK1 (P-SPK1) cell signaling, but ATV could increase P-MEK and P-ERK protein expression; (4) ATV has a beneficial effect on LPS-induced myocarditis via inhibition of P-AKT2/SPK1-mediated macrophage recruitment, apoptosis, TNFα, IL-1β, and IL-6; (5) ATV-offered protection against LPS-induced myocarditis was eliminated from SPK1-KO mice; (6) SPK1 may play a harmful role in LPS-induced myocarditis. Taken together, our data revealed that SPK1 represents a novel regulating factor for macrophage migration and cardiac protection under LPS-induced myocarditis.

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References

Cho H, Mu J, Kim J, Thorvaldsen J, Chu Q, Crenshaw 3rd E . Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science. 2001; 292(5522):1728-31. DOI: 10.1126/science.292.5522.1728. View

Liu H, Tao L, Gao E, Lopez B, Christopher T, Willette R . Anti-apoptotic effects of rosiglitazone in hypercholesterolemic rabbits subjected to myocardial ischemia and reperfusion. Cardiovasc Res. 2004; 62(1):135-44. DOI: 10.1016/j.cardiores.2003.12.027. View

Tavener S, Long E, Robbins S, McRae K, Van Remmen H, Kubes P . Immune cell Toll-like receptor 4 is required for cardiac myocyte impairment during endotoxemia. Circ Res. 2004; 95(7):700-7. DOI: 10.1161/01.RES.0000144175.70140.8c. View

Allende M, Sasaki T, Kawai H, Olivera A, Mi Y, van Echten-Deckert G . Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. J Biol Chem. 2004; 279(50):52487-92. DOI: 10.1074/jbc.M406512200. View

Pleger S, Remppis A, Heidt B, Volkers M, Chuprun J, Kuhn M . S100A1 gene therapy preserves in vivo cardiac function after myocardial infarction. Mol Ther. 2005; 12(6):1120-9. DOI: 10.1016/j.ymthe.2005.08.002. View

Jin Z, Karliner J . Low dose N, N-dimethylsphingosine is cardioprotective and activates cytosolic sphingosine kinase by a PKCepsilon dependent mechanism. Cardiovasc Res. 2006; 71(4):725-34. DOI: 10.1016/j.cardiores.2006.06.010. View

Funakoshi H, Zacharia L, Tang Z, Zhang J, Lee L, Good J . A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine levels in mice with left ventricular dysfunction. Circulation. 2007; 115(17):2307-15. DOI: 10.1161/CIRCULATIONAHA.107.694596. View

Shiraya S, Miyake T, Aoki M, Yoshikazu F, Ohgi S, Nishimura M . Inhibition of development of experimental aortic abdominal aneurysm in rat model by atorvastatin through inhibition of macrophage migration. Atherosclerosis. 2008; 202(1):34-40. DOI: 10.1016/j.atherosclerosis.2008.03.020. View

Iwasaki K, Kojima K, Kodama S, Paz A, Chambers M, Umezu M . Bioengineered three-layered robust and elastic artery using hemodynamically-equivalent pulsatile bioreactor. Circulation. 2008; 118(14 Suppl):S52-7. DOI: 10.1161/CIRCULATIONAHA.107.757369. View

10.

Li X, Mikhalkova D, Gao E, Zhang J, Myers V, Zincarelli C . Myocardial injury after ischemia-reperfusion in mice deficient in Akt2 is associated with increased cardiac macrophage density. Am J Physiol Heart Circ Physiol. 2011; 301(5):H1932-40. PMC: 3213957. DOI: 10.1152/ajpheart.00755.2010. View

11.

Xu P, Yu H, Zhang Z, Meng Q, Sun H, Chen X . Hydrogen-bonded and reduction-responsive micelles loading atorvastatin for therapy of breast cancer metastasis. Biomaterials. 2014; 35(26):7574-87. DOI: 10.1016/j.biomaterials.2014.05.030. View

12.

Pineda-Torra I, Gage M, de Juan A, Pello O . Isolation, Culture, and Polarization of Murine Bone Marrow-Derived and Peritoneal Macrophages. Methods Mol Biol. 2015; 1339:101-9. DOI: 10.1007/978-1-4939-2929-0_6. View

13.

Suffredini A, Fromm R, Parker M, Brenner M, Kovacs J, Wesley R . The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med. 1989; 321(5):280-7. DOI: 10.1056/NEJM198908033210503. View

14.

Yang N, Cheng W, Hu H, Xue M, Li X, Wang Y . Atorvastatin attenuates sympathetic hyperinnervation together with the augmentation of M2 macrophages in rats postmyocardial infarction. Cardiovasc Ther. 2016; 34(4):234-44. DOI: 10.1111/1755-5922.12193. View

15.

Shi Y, Lai X, Ye L, Chen K, Cao Z, Gong W . Activated niacin receptor HCA2 inhibits chemoattractant-mediated macrophage migration via Gβγ/PKC/ERK1/2 pathway and heterologous receptor desensitization. Sci Rep. 2017; 7:42279. PMC: 5301212. DOI: 10.1038/srep42279. View

16.

Ma W, Wang Y, Lu S, Yan L, Hu F, Wang Z . Targeting androgen receptor with ASC-J9 attenuates cardiac injury and dysfunction in experimental autoimmune myocarditis by reducing M1-like macrophage. Biochem Biophys Res Commun. 2017; 485(4):746-752. DOI: 10.1016/j.bbrc.2017.02.123. View

17.

Yang Y, Zhao J, Zhang J, Lei Y, Yuan F, Liu L . Regulation of macrophage migration in ischemic mouse hearts via an AKT2/NBA1/SPK1 pathway. Oncotarget. 2018; 8(70):115345-115359. PMC: 5777776. DOI: 10.18632/oncotarget.23263. View