Class I PI3K inhibitor ZSTK474 mediates a shift in microglial/macrophage phenotype and inhibits inflammatory response in mice with cerebral ischemia/reperfusion injury

Journal of Neuroinflammation

Volumn 13, Issue 1, 2016, Pages

  Wang, Po ^a,b   He, Yating ^a   Li, Daojing ^a   Han, Ranran ^a   Liu, Guiyou ^c   Kong, Dexin ^a   Hao, Junwei ^a  

^a TIANJIN MEDICAL UNIVERSITY   (China)

^b BAOTOU CENTRAL HOSPITAL   (China)

^c Tianjin Airport Economic Area   (China)

Author keywords

Cerebral ischemia reperfusion injury; Inflammation; Microglia macrophages; PI3K AKT mTORC1 pathway; ZSTK474

Indexed keywords

2 (2 DIFLUOROMETHYLBENZIMIDAZOL 1 YL) 4,6 DIMORPHOLINO 1,3,5 TRIAZINE; CALCIUM BINDING PROTEIN; CD16 ANTIGEN; CD32 ANTIGEN; GLIAL FIBRILLARY ACIDIC PROTEIN; INTERLEUKIN 10; INTERLEUKIN 1BETA; IONIZED CALCIUM BINDING ADAPTOR MOLECULE 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN P70; S6 KINASE; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; ANTIINFLAMMATORY AGENT; CYTOKINE; INDUCIBLE NITRIC OXIDE SYNTHASE; LEUKOCYTE ANTIGEN; TRIAZINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BRAIN INFARCTION SIZE; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DISEASE SEVERITY; DOWN REGULATION; DRUG EFFICACY; ENZYME PHOSPHORYLATION; GENE EXPRESSION; MALE; MIDDLE CEREBRAL ARTERY OCCLUSION; MOUSE; NEUROPROTECTION; NONHUMAN; PROTEIN DETERMINATION; PROTEIN EXPRESSION; ANIMAL; BRAIN INFARCTION; BRAIN ISCHEMIA; C57BL MOUSE; COMPLICATION; DISEASE MODEL; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; INFLAMMATION; MACROPHAGE; METABOLISM; MICROGLIA; NERVOUS SYSTEM DISEASES; PATHOLOGY; REPERFUSION INJURY; SIGNAL TRANSDUCTION;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTIGENS, CD; BRAIN INFARCTION; BRAIN ISCHEMIA; CYTOKINES; DISEASE MODELS, ANIMAL; GENE EXPRESSION REGULATION; GLIAL FIBRILLARY ACIDIC PROTEIN; INFLAMMATION; MACROPHAGES; MALE; MICE; MICE, INBRED C57BL; MICROGLIA; NERVOUS SYSTEM DISEASES; NITRIC OXIDE SYNTHASE TYPE II; REPERFUSION INJURY; SIGNAL TRANSDUCTION; TRIAZINES;

EID: 84983247012     PISSN: None     EISSN: 17422094     Source Type: Journal    
DOI: 10.1186/s12974-016-0660-1     Document Type: Article

References (39)

1. Schellinger PD, Kaste M, Hacke W. An update on thrombolytic therapy for acute stroke. Curr Opin Neurol. 2004;17:69-77.
2. Pandya RS, Mao L, Zhou H, Zhou S, Zeng J, Popp AJ, Wang X. Central nervous system agents for ischemic stroke: neuroprotection mechanisms. Cent Nerv Syst Agents Med Chem. 2011;11:81-97.
3. Williams-Karnesky RL, Stenzel-Poore MP. Adenosine and stroke: maximizing the therapeutic potential of adenosine as a prophylactic and acute neuroprotectant. Curr Neuropharmacol. 2009;7:217-27.
4. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41:14-20.
5. Stout RD, Jiang C, Matta B, Tietzel I, Watkins SK, Suttles J. Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences. J Immunol. 2005;175:342-9.
6. Yenari MA, Kauppinen TM, Swanson RA. Microglial activation in stroke: therapeutic targets. Neurotherapeutics. 2010;7:378-91.
7. Yaguchi S, Fukui Y, Koshimizu I, Yoshimi H, Matsuno T, Gouda H, Hirono S, Yamazaki K, Yamori T. Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor. Int J Natl Cancer Inst. 2006;98:545-56.
8. Kong D, Yaguchi S, Yamori T. Effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor, on DNA-dependent protein kinase. Biol Pharm Bull. 2009;32:297-300.
9. Kong D, Yamori T. ZSTK474 is an ATP-competitive inhibitor of class I phosphatidylinositol 3 kinase isoforms. Cancer Sci. 2007;98:1638-42.
10. Kong DX, Yamori T. ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor identified using the JFCR39 drug discovery system. Acta Pharmacol Sin. 2010;31:1189-97.
11. Haruta K, Mori S, Tamura N, Sasaki A, Nagamine M, Yaguchi S, Kamachi F, Enami J, Kobayashi S, Yamori T, Takasaki Y. Inhibitory effects of ZSTK474, a phosphatidylinositol 3-kinase inhibitor, on adjuvant-induced arthritis in rats. Inflamm Res. 2012;61:551-62.
12. Toyama S, Tamura N, Haruta K, Karakida T, Mori S, Watanabe T, Yamori T, Takasaki Y. Inhibitory effects of ZSTK474, a novel phosphoinositide 3-kinase inhibitor, on osteoclasts and collagen-induced arthritis in mice. Arthritis Res Ther. 2010;12:R92.
13. Xue Z, Li W, Wang H, Huang B, Ge Z, Gu C, Liu Y, Zhang K, Yang J, Han R, et al. ZSTK474, a novel PI3K inhibitor, modulates human CD14+ monocyte-derived dendritic cell functions and suppresses experimental autoimmune encephalomyelitis. J Mol Med (Berl). 2014;92:1057-68.
14. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20:84-91.
15. Chen J, Sanberg PR, Li Y, Wang L, Lu M, Willing AE, Sanchez-Ramos J, Chopp M. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke. 2001;32:2682-8.
16. Ban JY, Kang SW, Lee JS, Chung JH, Ko YG, Choi HS. Korean red ginseng protects against neuronal damage induced by transient focal ischemia in rats. Exp Ther Med. 2012;3:693-8.
17. Bouet V, Boulouard M, Toutain J, Divoux D, Bernaudin M, Schumann-Bard P, Freret T. The adhesive removal test: a sensitive method to assess sensorimotor deficits in mice. Nat Protoc. 2009;4:1560-4.
18. Freret T, Bouet V, Leconte C, Roussel S, Chazalviel L, Divoux D, Schumann-Bard P, Boulouard M. Behavioral deficits after distal focal cerebral ischemia in mice: usefulness of adhesive removal test. Behav Neurosci. 2009;123:224-30.
19. Zhang Y, Xing S, Zhang J, Li J, Li C, Pei Z, Zeng J. Reduction of beta-amyloid deposits by gamma-secretase inhibitor is associated with the attenuation of secondary damage in the ipsilateral thalamus and sensory functional improvement after focal cortical infarction in hypertensive rats. J Cereb Blood Flow Metab. 2011;31:572-9.
20. Zhou Y, Lekic T, Fathali N, Ostrowski RP, Martin RD, Tang J, Zhang JH. Isoflurane posttreatment reduces neonatal hypoxic-ischemic brain injury in rats by the sphingosine-1-phosphate/phosphatidylinositol-3-kinase/Akt pathway. Stroke. 2010;41:1521-7.
21. Yao Y, Chen L, Xiao J, Wang C, Jiang W, Zhang R, Hao J. Chrysin protects against focal cerebral ischemia/reperfusion injury in mice through attenuation of oxidative stress and inflammation. Int J Mol Sci. 2014;15:20913-26.
22. Liu Z, Chopp M. Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke. Prog Neurobiol.2015; doi: 10.1016/j.pneurobio.2015.09.008.
23. Kim JY, Kim N, Yenari MA. Mechanisms and potential therapeutic applications of microglial activation after brain injury. CNS Neurosci Ther. 2015;21:309-19.
24. Wang M, Wang Y, He J, Wei S, Zhang N, Liu F, Liu X, Kang Y, Yao X. Albumin induces neuroprotection against ischemic stroke by altering Toll-like receptor 4 and regulatory T cells in mice. CNS Neurol Disord Drug Targets. 2013;12:220-7.
25. Bronte V, Murray PJ. Understanding local macrophage phenotypes in disease: modulating macrophage function to treat cancer. Nat Med. 2015;21:117-9.
26. Zhou H, Chen S, Wang W, Wang Z, Wu X, Zhang Z. Nanog inhibits lipopolysaccharide-induced expression of pro-inflammatory cytokines by blocking NF-kappaB transcriptional activity in rat primary microglial cells. Mol Med Rep. 2012;5:842-6.
27. Vila N, Castillo J, Davalos A, Chamorro A. Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke. 2000;31:2325-9.
28. Tikka T, Fiebich BL, Goldsteins G, Keinanen R, Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci. 2001;21:2580-8.
29. Hedrich CM, Bream JH. Cell type-specific regulation of IL-10 expression in inflammation and disease. Immunol Res. 2010;47:185-206.
30. Nathan C, Ding A. Nonresolving inflammation. Cell. 2010;140:871-82.
31. Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol. 2009;10:307-18.
32. Wang G, Shi Y, Jiang X, Leak RK, Hu X, Wu Y, Pu H, Li WW, Tang B, Wang Y, et al. HDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3beta/PTEN/Akt axis. Proc Natl Acad Sci U S A. 2015;112:2853-8.
33. Xie L, Sun F, Wang J, Mao X, Xie L, Yang SH, Su DM, Simpkins JW, Greenberg DA, Jin K. mTOR signaling inhibition modulates macrophage/microglia-mediated neuroinflammation and secondary injury via regulatory T cells after focal ischemia. J Immunol. 2014;192:6009-19.
34. de Oliveira AC, Candelario-Jalil E, Langbein J, Wendeburg L, Bhatia HS, Schlachetzki JC, Biber K, Fiebich BL. Pharmacological inhibition of Akt and downstream pathways modulates the expression of COX-2 and mPGES-1 in activated microglia. J Neuroinflammation. 2012;9:2.
35. Tarassishin L, Suh HS, Lee SC. Interferon regulatory factor 3 plays an anti-inflammatory role in microglia by activating the PI3K/Akt pathway. J Neuroinflammation. 2011;8:187.
36. Dong H, Zhang X, Dai X, Lu S, Gui B, Jin W, Zhang S, Zhang S, Qian Y. Lithium ameliorates lipopolysaccharide-induced microglial activation via inhibition of toll-like receptor 4 expression by activating the PI3K/Akt/FoxO1 pathway. J Neuroinflammation. 2014;11:140.
37. Li W, Yang Y, Hu Z, Ling S, Fang M. Neuroprotective effects of DAHP and Triptolide in focal cerebral ischemia via apoptosis inhibition and PI3K/Akt/mTOR pathway activation. Front Neuroanat. 2015;9:48.
38. Low PC, Manzanero S, Mohannak N, Narayana VK, Nguyen TH, Kvaskoff D, Brennan FH, Ruitenberg MJ, Gelderblom M, Magnus T, et al. PI3Kdelta inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model. Nat Commun. 2014;5:3450.
39. Ruckle T, Schwarz MK, Rommel C. PI3Kgamma inhibition: towards an 'aspirin of the 21st century'? Nat Rev Drug Discov. 2006;5:903-18.