The Expression and Significance of PTEN in Peripheral Blood Mononuclear Cells of Patients with Sepsis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 CHENGZheng-jun ¹ ,  HEZhong-lin ²

1. Department of General Surgery, The Second People's Hospital of Jiulongpo District, Chongqing 400052, China;
2. First Zone of General Surgery Department, The Ninth People's Hospital of Chongqing, Chongqing 400700, China;

Corresponding author：

HEZhong-lin, Email: hezhonglinxin@163.com

Keywords：

Sepsis; Phosphatase gene protein; Inhibitor of nuclear fator-κB

DOI：

10.7507/1007-9424.20160319

Video：

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Objective To detecte the expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene and protein in peripheral blood mononuclear cells (PBMC) of patients with sepsis and to explore its role in the pathogenesis of acute obstructive suppurative cholangitis (AOSC). Methods The PBMC and serum were separated from AOSC patients (n=25) before treatment and in 1 week after recure, and healthy volunteers (normal control group, n=15). The serum levels of lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10) were detected by enzyme linked immunosorbent assay (ELISA) methods. The mRNA and protein expression levels of PTEN, nuclear fator κB P65 (NF-κB), and inhibitor of NF-κB (IκB) were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, respectively. Results The levels of LPS, TNF-α, and IL-10 before treatment were significantly higher than those of normal control group (P < 0.05), the indicators were significantly decreased and close to normal levels in 1 week after recure. The mRNA and protein expression levels of PTEN and IκB before treatment were lower than those of normal control group (P < 0.05), NF-κB P65 was higher than those of normal control group (P < 0.05), while the phosphorylation levels of PTEN and IκB were higher than those normal control group (P < 0.05), and in 1 week after recure, the above indicators returned to normal levels. Conclusions Sepsis shift may be associated with the occurrence of intestinal LPS, and caused the imbalance between proinflammatory and anti-inflammatory cytokines in the body. PTEN for phosphorylation activation of IκB or directly activation of NF-κB participate the originating process of sepsis, hinting a therapeutic potentialities in the early stage of sepsis.

Citation： CHENG Zheng-jun, HE Zhong-lin. The Expression and Significance of PTEN in Peripheral Blood Mononuclear Cells of Patients with Sepsis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2016, 23(10): 1243-1248. doi: 10.7507/1007-9424.20160319 Copy

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2.	Gohil SK, Cao C, Phelan M, et al. Impact of policies on the rise in sepsis incidence, 2000-2010. Clin Infect Dis, 2016, 62(6):695-703.
3.	O'Callaghan EK, Anderson ST, Moynagh PN, et al. Long-lasting effects of sepsis on circadian rhythms in the mouse. PLoS One, 2012, 7(10):e47087.
4.	Anderson ST, Commins S, Moynagh PN, et al. Lipopolysaccharide-induced sepsis induces long-lasting affective changes in the mouse. Brain Behav Immun, 2015, 43:98-109.
5.	Liu Z, Shi Q, Liu J, et al. Innate immune molecule surfactant protein D attenuates sepsis-induced acute pancreatic injury through modulating apoptosis and NF-κB-mediated inflammation. Sci Rep, 2015, 5:17798.
6.	Hoogland IC, Houbolt C, van Westerloo DJ, et al. Systemic inflammation and microglial activation:systematic review of animal experiments. J Neuroinflammation, 2015, 12:114.
7.	Ghosh S, Dass JF. Study of pathway cross-talk interactions with NF-κB leading to its activation via ubiquitination or phosphorylation:A brief review. Gene, 2016, 584(1):97-109.
8.	Dyson HJ, Wright PE. Role of intrinsic protein disorder in the function and interactions of the transcriptional coactivators CREB-binding protein (CBP) and p300. J Biol Chem, 2016, 291(13):6714-6722.
9.	Sartor RB. Review article:the potential mechanisms of action of rifaximin in the management of inflammatory bowel diseases. Aliment Pharmacol Ther, 2016, 43 Suppl 1:27-36.
10.	Nold-Petry CA, Lo CY, Rudloff I, et al. IL-37 requires the receptors IL-18Rα and IL-1R8(SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction. Nat Immunol, 2015, 16(4):354-365.
11.	Zhou Y, Yang Q, Xu H, et al. miRNA-221-3p enhances the secretion of interleukin-4 in mast cells through the phosphatase and tensin homolog/p38/nuclear factor-kappaB pathway. PLoS One, 2016, 11(2):e0148821.
12.	Takada T, Strasberg SM, Solomkin JS, et al. TG13:Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci, 2013, 20(1):1-7.
13.	中华医学会重症医学分会. 中国严重脓毒症/脓毒性休克治疗指南(2014). 中华内科杂志, 2015, 54(6):557-581.
14.	Zhang J, Nie X, Boquel S, et al. Increased sensitivity of RT-PCR for Potato virus Y detection using RNA isolated by a procedure with differential centrifugation. J Virol Methods, 2015, 225:49-54.
15.	Feretzaki M, Lingner J. A practical qPCR approach to detect TERRA, the elusive telomeric repeat-containing RNA. Methods, 2016.[Epub ahead of print].
16.	Johnson DL, Stiles BL. Maf1, a new PTEN target linking RNA and lipid metabolism. Trends Endocrinol Metab, 2016.[Epub ahead of print].
17.	Shojaee S, Chan LN, Buchner M, et al. PTEN opposes negative selection and enables oncogenic transformation of pre-B cells. Nat Med, 2016.[Epub ahead of print].
18.	Li S, Zhu M, Pan R, et al. The tumor suppressor PTEN has a critical role in antiviral innate immunity. Nat Immunol, 2016, 17(3):241-249.
19.	Kamo N, Ke B, Busuttil RW, et al. PTEN-mediated Akt/β-catenin/Foxo1 signaling regulates innate immune responses in mouse liver ischemia/reperfusion injury. Hepatology, 2013, 57(1):289-298.
20.	Leslie NR, Kriplani N, Hermida MA, et al. The PTEN protein:cellular localization and post-translational regulation. Biochem Soc Trans, 2016, 44(1):273-278.
21.	Martin M, Rehani K, Jope RS, et al. Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol, 2005, 6(8):777-784.
22.	Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol, 2012, 13(5):283-296.
23.	Wang B, Wang D, Yan T, et al. MiR-138-5p promotes TNF-α-induced apoptosis in human intervertebral disc degeneration by targeting SIRT1 through PTEN/PI3K/Akt signaling. Exp Cell Res, 2016, 345(2):199-205.
24.	Wu C, Xue Y, Wang P, et al. IFN-γ primes macrophage activation by increasing phosphatase and tensin homolog via downregulation of miR-3473b. J Immunol, 2014, 193(6):3036-3044.
25.	Sordi R, Chiazza F, Johnson FL, et al. Inhibition of IκB kinase attenuates the organ injury and dysfunction associated with hemorrhagic shock. Mol Med, 2015, 21:563-575.
26.	Im E, Jung J, Pothoulakis C, et al. Disruption of pten speeds onset and increases severity of spontaneous colitis in IL10-/-mice. Gastro-enterology, 2014, 147(3):667-679.
27.	Hua FZ, Ying J, Zhang J, et al. Naringenin pre-treatment inhibits neuroapoptosis and ameliorates cognitive impairment in rats exposed to isoflurane anesthesia by regulating the PI3/Akt/PTEN signalling pathway and suppressing NF-κB-mediated inflammation. Int J Mol Med, 2016.[Epub ahead of print].

1. Stevenson EK, Rubenstein AR, Radin GT, et al. Two decades of mortality trends among patients with severe sepsis:a comparative meta-analysis. Crit Care Med, 2014, 42(3):625-631.
2. Gohil SK, Cao C, Phelan M, et al. Impact of policies on the rise in sepsis incidence, 2000-2010. Clin Infect Dis, 2016, 62(6):695-703.
3. O'Callaghan EK, Anderson ST, Moynagh PN, et al. Long-lasting effects of sepsis on circadian rhythms in the mouse. PLoS One, 2012, 7(10):e47087.
4. Anderson ST, Commins S, Moynagh PN, et al. Lipopolysaccharide-induced sepsis induces long-lasting affective changes in the mouse. Brain Behav Immun, 2015, 43:98-109.
5. Liu Z, Shi Q, Liu J, et al. Innate immune molecule surfactant protein D attenuates sepsis-induced acute pancreatic injury through modulating apoptosis and NF-κB-mediated inflammation. Sci Rep, 2015, 5:17798.
6. Hoogland IC, Houbolt C, van Westerloo DJ, et al. Systemic inflammation and microglial activation:systematic review of animal experiments. J Neuroinflammation, 2015, 12:114.
7. Ghosh S, Dass JF. Study of pathway cross-talk interactions with NF-κB leading to its activation via ubiquitination or phosphorylation:A brief review. Gene, 2016, 584(1):97-109.
8. Dyson HJ, Wright PE. Role of intrinsic protein disorder in the function and interactions of the transcriptional coactivators CREB-binding protein (CBP) and p300. J Biol Chem, 2016, 291(13):6714-6722.
9. Sartor RB. Review article:the potential mechanisms of action of rifaximin in the management of inflammatory bowel diseases. Aliment Pharmacol Ther, 2016, 43 Suppl 1:27-36.
10. Nold-Petry CA, Lo CY, Rudloff I, et al. IL-37 requires the receptors IL-18Rα and IL-1R8(SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction. Nat Immunol, 2015, 16(4):354-365.
11. Zhou Y, Yang Q, Xu H, et al. miRNA-221-3p enhances the secretion of interleukin-4 in mast cells through the phosphatase and tensin homolog/p38/nuclear factor-kappaB pathway. PLoS One, 2016, 11(2):e0148821.
12. Takada T, Strasberg SM, Solomkin JS, et al. TG13:Updated Tokyo Guidelines for the management of acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci, 2013, 20(1):1-7.
13. 中华医学会重症医学分会. 中国严重脓毒症/脓毒性休克治疗指南(2014). 中华内科杂志, 2015, 54(6):557-581.
14. Zhang J, Nie X, Boquel S, et al. Increased sensitivity of RT-PCR for Potato virus Y detection using RNA isolated by a procedure with differential centrifugation. J Virol Methods, 2015, 225:49-54.
15. Feretzaki M, Lingner J. A practical qPCR approach to detect TERRA, the elusive telomeric repeat-containing RNA. Methods, 2016.[Epub ahead of print].
16. Johnson DL, Stiles BL. Maf1, a new PTEN target linking RNA and lipid metabolism. Trends Endocrinol Metab, 2016.[Epub ahead of print].
17. Shojaee S, Chan LN, Buchner M, et al. PTEN opposes negative selection and enables oncogenic transformation of pre-B cells. Nat Med, 2016.[Epub ahead of print].
18. Li S, Zhu M, Pan R, et al. The tumor suppressor PTEN has a critical role in antiviral innate immunity. Nat Immunol, 2016, 17(3):241-249.
19. Kamo N, Ke B, Busuttil RW, et al. PTEN-mediated Akt/β-catenin/Foxo1 signaling regulates innate immune responses in mouse liver ischemia/reperfusion injury. Hepatology, 2013, 57(1):289-298.
20. Leslie NR, Kriplani N, Hermida MA, et al. The PTEN protein:cellular localization and post-translational regulation. Biochem Soc Trans, 2016, 44(1):273-278.
21. Martin M, Rehani K, Jope RS, et al. Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol, 2005, 6(8):777-784.
22. Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol, 2012, 13(5):283-296.
23. Wang B, Wang D, Yan T, et al. MiR-138-5p promotes TNF-α-induced apoptosis in human intervertebral disc degeneration by targeting SIRT1 through PTEN/PI3K/Akt signaling. Exp Cell Res, 2016, 345(2):199-205.
24. Wu C, Xue Y, Wang P, et al. IFN-γ primes macrophage activation by increasing phosphatase and tensin homolog via downregulation of miR-3473b. J Immunol, 2014, 193(6):3036-3044.
25. Sordi R, Chiazza F, Johnson FL, et al. Inhibition of IκB kinase attenuates the organ injury and dysfunction associated with hemorrhagic shock. Mol Med, 2015, 21:563-575.
26. Im E, Jung J, Pothoulakis C, et al. Disruption of pten speeds onset and increases severity of spontaneous colitis in IL10-/-mice. Gastro-enterology, 2014, 147(3):667-679.
27. Hua FZ, Ying J, Zhang J, et al. Naringenin pre-treatment inhibits neuroapoptosis and ameliorates cognitive impairment in rats exposed to isoflurane anesthesia by regulating the PI3/Akt/PTEN signalling pathway and suppressing NF-κB-mediated inflammation. Int J Mol Med, 2016.[Epub ahead of print].

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The Expression and Significance of PTEN in Peripheral Blood Mononuclear Cells of Patients with Sepsis

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