Associations of Toll-like receptors mRNA expressions and their downstream signaling pathways in peripheral blood mononuclear cells with clinical outcomes in patients with cerebral infarction

Abstract

Objective To investigate the associations of Toll-like receptors (TLRs) mRNA expressions and their downstream signaling pathways in peripheral blood mononuclear cells with clinical outcomes in patients with cerebral infarction. Methods Ninety patients with cerebral infarction of anterior circulation, admitted to our hospital from May 2015 to December 2015, were chosen. Quantitative real-time PCR was performed to measure the expressions of TLR2, TLR4, TLR3, TLR7, TLR8 and TLR9 and downstream signaling molecules Toll-like receptors related molecule (TRAM), interferon regulatory factor 3 (IRF-3), and interferon beta (IFN-β) in peripheral blood mononuclear cells. Good functional outcome was defined as modified Rankin Scale (mRS) scores≤2 90 d after onset. National Institutes of Health Stroke Scale (NIHSS) on admission was used to evaluate the severity of stroke, and infarct volume 7-14 d after onset was measured on MR imaging. The baseline characteristics (TLRs, population information, risk factors, stroke types, clinical and imaging data) were compared between patients with good and bad functional outcomes. Multi-factor Logistics regression analysis was performed. Results TLR3 and TLR7 mRNA expressions were correlated with good functional outcome at acute cerebral infarction, and only TLR3 expression was correlated with good functional outcome at sub-acute phase. TLR3 mRNA expression, Creactive protein (CRP) level, and NIHSS scores on admission were positively correlated with good outcome (OR=4.435, P=0.001; OR= 1.12, P=0.033; OR=1.961, P=0.000). The expressions of TLR3 and IRF-3 were both inversely correlated with NIHSS scores and cerebral infarction volume; IFN-β mRNA expression was positively correlated to TLR3 expression (r=0.392, P=0.000); IFN-β expression and IRF level were positively correlated (r=0.347, P=0.01). Conclusion The TLR3 expression is correlated with good functional outcome in peripheral blood mononuclear cells of patients with cerebral infarction, which may play a crucial role in the survival of neurons after ischemia through spuring the extraction of anti-inflammatory factor IFN-β. Key words: Cerebral infarction; Toll-like receptors; Clinical outcome; Toll-like receptor 3; Interferon beta