Elevated Tumor Necrosis Factor-a-induced Protein 8-like 2 mRNA from Peripheral Blood Mononuclear Cells in Patients with Acute Ischemic Stroke

Abstract

Background: Tumor necrosis factor-a-induced protein 8-like 2 (TIPE2) is a novel regulator of immunity and protects against experimental stroke. However, the expression and function of TIPE2 in patients with acute ischemic stroke has not been well demonstrated.Methods: A total of 182 consecutive patients with acute ischemic stroke and 40 healthy controls were included during November 2015 to June 2016. The mRNA levels of TIPE2, interleukin(IL)-1β, IL-10, IL-6, nuclear factor(NF)-κβ, activator protein(AP)-1, interferon(IFN)-γ and tumor necrosis factor(TNF)-α from peripheral blood mononuclear cells were determined using real time quantitative reverse transcriptase polymerase chain reaction. The severity of stroke was assessed using the National Institutes of Health Stroke Scale (NIHSS) score.Results: The median mRNA levels of TIPE2, TNF-α, AP-1, IFN-γ and NF-κβ in patients with acute ischemic stroke were significantly higher than healthy controls (all P<0.001, respectively). Of note, TIPE2 mRNA showed an increasing trend on a time-dependent manner after the onset of stroke. Furthermore, TIPE2 mRNA was negatively associated with lesion volumes (r=-0.23, P<0.01), NIHSS(r=-0.15, P<0.05), TNF-α(r=-0.33,P<0.001), AP-1(r=-0.28,P<0.001), IFN-γ (r=-0.16, P<0.05) and NF-κβ (r=-0.13, P<0.05), but positively associated with IL-6(r=0.14, P<0.05) and IL-10(r=-0.31, P<0.001). Hierarchy cluster analysis showed that TIPE2 mRNA has nearest membership with TNF-α, followed by IL-6, NF-κβ, AP-1, IL-10, IL-1β and IFN-γ. In addition, TIPE2 mRNA in survivals (n=149) was significantly higher than nonsurvivals (n=33) (P<0.001), and showed a great odd ratio (0.52, 95% confidence interval: 0.349-0.760, P<0.001) on 3-month mortality.Conclusions: TIPE2 mRNA contributed to the immune response of stroke and might be a potential biomarker for the mortality of acute ischemic stroke.

<p>Regulatory Roles of Tumor Necrosis Factor-α-Induced Protein 8 Like-Protein 2 in Inflammation, Immunity and Cancers: A Review</p>

“… 70 Another study demonstrated that TIPE2 mRNA expression in survivors was much higher than that in dead, showing a prominent odds ratio on 3-month mortality. 71 These findings implied that TIPE2 regulated inflammatory responses of stroke and showed an important neuroprotective effect on brain cells, suggesting its potential as a diagnostic and prognostic biomarker for acute ischemic stroke. 70 , 71 Moreover, TIPE2 was also capable of modulating inflammation intensity by regulating macrophage polarization via suppressing mammalian target of rapamycin complex1 (mTORC1) activation.…”

“… 71 These findings implied that TIPE2 regulated inflammatory responses of stroke and showed an important neuroprotective effect on brain cells, suggesting its potential as a diagnostic and prognostic biomarker for acute ischemic stroke. 70 , 71 Moreover, TIPE2 was also capable of modulating inflammation intensity by regulating macrophage polarization via suppressing mammalian target of rapamycin complex1 (mTORC1) activation. 72 Interestingly, TIPE2 null mice were susceptible to pseudomonas aeruginosa (PA) infection and showed serious keratitis.…”

Serum Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 Associated with the Severity and Outcome of Acute Ischemic Stroke

“…Therefore, proinflammatory cytokines, including TNFα, IL-6, and sTREM-1, leaked into peripheral circulation from CSF through disrupted BBB. Proinflammatory cytokines in the acute-phase response, particularly TNFα and IL-6, were found to be associated with early clinical neurological deterioration and long-term outcomes, after acute ischemic stroke [ 11 , 19 , 53 , 54 , 55 ]. In the present study, the higher serum level of sTREM-1 may be regarded as a serum biomarker that reflects the severity of innate inflammation and poor prognosis in patients, after acute ischemic stroke.…”

Elevated repulsive guidance molecule-a mRNA in peripheral blood mononuclear cells are associated with impaired leptomeningeal collaterals in patients with middle cerebral artery occlusions

“…Gene expression changes in peripheral mononuclear cells (PBMCs) have been observed in patients with ischemic stroke, suggesting these genes hold potential for diagnostic biomarker in these patients (8)(9)(10). Thus, probe for potential genetic parameters in PBMCs may be clinically useful in predicting the LMCs status in MCAO patients.…”