Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and septic shock in a Chinese Han population

BACKGROUND: Triggering receptor expressed on myeloid cells-1(TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify infl ammation and serves as a critical mediator of infl ammatory response in the context of sepsis. To date, the predisposition of TREM-1 gene polymorphisms to septic shock has not been reported. This study was designed to investigate whether TREM-1 genomic variations are associated with the development of septic shock.METHODS: We genotyped two TREM-1 single nucleotide polymorphisms(SNPs, rs2234237 and rs2234246) and evaluated the relationships between these SNPs and septic shock on susceptibility and prognosis.RESULTS: TREM-1 rs2234246 A allele in the promoter region was signifi cantly associated with the susceptibility of septic shock in recessive model(AA, OR=3.10, 95%CI 1.15 to 8.32, P=0.02), and in codominant model(AG, OR=0.72, 95%CI 0.43–1.19, P=0.02; AA, OR=2.71, 95%CI 1.00–7.42; P=0.03). However, in three inherited models(dominant model, recessive model, and codominant model), none of the assayed loci was signif icantly associated with the prognosis of septic shock. The nonsurvivor group demonstrated higher plasma IL-6 levels(99.7±34.7 pg/mL vs. 61.2±26.5 pg/mL, P<0.01) than the survivor group. Plasma concentrations of IL-6 among the three genotypes of rs2234246 were AA 99.4±48.9 pg/m L, AG 85.4±43 pg/m L, and GG 65.3±30.7 pg/m L(P<0.01). The plasma concentrations of IL-6 in patients with AA genotypes were signifi cantly higher than those in patients with GG genotypes(P<0.01).CONCLUSION: TREM-1 genetic polymorphisms rs2234246 may be significantly correlated only with susceptibility to septic shock in the Chinese Han population.

Relationship between expression of triggering receptor-1 on myeloid cells in intestinal tissue and intestinal barrier dysfunction in severe acute pancreatitis

BACKGROUND：Triggering receptor expressed on myeloid cells-1 （TREM-1） in the intestine was upregulated and correlated with disease activity in inflammatory bowel diseases. Membrane- bound TREM-1 protein is increased in the pancreas, liver and kidneys of patients with severe acute pancreatitis （SAP）, suggesting that TREM-1 may act as an important mediator of inflammation and subsequent extra-pancreatic organ injury. This study aimed to investigate the relationship between the expression of TREM-1 in intestinal tissue and intestinal barrier dysfunction in SAP. METHODS： Sixty-four male Wistar rats were randomly divided into a sham operation group （SO group, n=32） and a SAP group （n=32）. A SAP model was established by retrograde injection of 5% sodium deoxycholate into the bile-pancreatic duct. Specimens were taken from blood and intestinal tissue 2, 6, 12, and 48 hours after operation respectively. The levels of D-lactate, diamine oxidase （DAO） and endotoxin in serum were measured using an improved spectro-photometric method. The expression levels of TREM-1, interleukin-1β （IL-1β）, and tumor necrosis factor-α （TNF-α） mRNA in terminal ileum were detected by real-time reverse transcription-polymerase chain reaction （RT-PCR）. Specimens of the distal ileum were taken to determine pathological changes by a validated histology score. The serum levels of D-lactate, DAO and endotoxin were significantly increased in each subgroup of SAP compared with the SO group （P〈0.01, P〈0.05）. The expression levels of TREM-1, IL-1β and TNF-a mRNA in the terminal ileum in each subgroup of SAP were significantly higher than those in the SO group （P〈0.01, P〈0.05）. The expression level of TREM-lmRNA was positively correlated with IL-1βand TNF-α mRNA （r=0.956, P=0.044; r=0.986, P=0.015）, but the correlation was not found between IL-1β mRNA and TNF-a mRNA （P=0.133）. Compared to the SO group, the pathological changes were aggravated significantly in the SAP group. CONCLUSIONS： The expression level of TREM-1 in intestinal tissue of rats with SAP was elevated, leading to the release of inflammatory mediators and intestinal mucosal injury. This finding indicates that TREM-I might play an important role in the development of intestinal barrier dysfunction in rats with SAP.

TREM-1 expression in rat corneal epithelium with Aspergillus fumigatus infection

AIM: To investigate the expression of triggering receptor expressed on myeloid cells-1(TREM-1) in the aberrant inflammation within the corneal epithelium at early period of fungal infection.METHODS: A total of 65 Wistar rats were randomly divided into control group, sham group and fungal keratitis(FK) group, in which the cornea was infected by Aspergillus fumigatus(A. fumigatus). After executed randomly at 8, 16, 24, 48 and 72 h after experimental model being established, the severity of keratomycosis in rats was scored visually with the aid of a dissecting microscope and slit lamp. Then corneas in three groups were collected to assess the expression of TREM-1through quantitative reverse transcription-polymerase chain reaction(RT-PCR), immunofluorescence technique and Western blot analysis. The correlation between FK inflammation and expression of TREM-1 was also analyzed.RESULTS: Corneal inflammation scores increased with time after fungal infection(F =49.74, P =0.000). The inflammation scores in FK group were obviously higher than those in sham group on the whole(F =137.78, P =0.000). Levels of TREM-1 in the infected rat corneal epithelium had elevated at 8h and peaked at 48h(P 【0.001,compared with control group). Western blot analysis also showed an obviously elevated TREM-1 level in rat corneal epithelium at 24 h and 48 h after fungal infection.Immunofluorescence technique showed that TREM-1mainly existed in corneal epithelium and infected corneal stoma of rat. TREM-1 protein expression was enhanced after fungal infection. Moreover, severity of FK inflammation was significantly related to TREM-1expression in FK(r =0.942, P =0.000).CONCLUSION: TREM-1 may contribute to amplify theinflammation in the cornea infected with A. fumigatus and play critical roles in the battle against A. fumigatus in the innate immune responses.

Soluble Triggering Receptor Expressed on Myeloid Cells-1 and Inflammatory Markers in Colorectal Cancer Surgery： A Prospective Cohort Study

Background： Major abdominal surgery, including colorectal cancer （CRC） surgery, leads to systemic inflammatory response syndrome that can be detected and monitored with inflammatory markers testing. The aims of the study were to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells-l （sTREM-1 ）, interleukin-6 （IL-6）, procalcitonin （PCT）, and C-reactive protein （CRP） in following the inflammatory response in CRC surgery and postoperative period, as well as to determine if duration of the surgery and the time that the colon has been opened during the surgery （open colon time [OCT]） refect a larger surgical stress through inflammatory markers rise. Methods： The study included 20 patients who underwent CRC surgery and 19 healthy volunteers from June 2011 to September 2012. We determined inflammatory markers 1 day before surgery （T0）, 24 h （T1）, 48 h （T2）, and 7 days after the surgery （T3）. All statistical analyses were calculated using MedCalc Statistical Software version 14.8.1 （MedCalc Software bvba, Ostend, Belgium）. Results： Concentrations ofCRP, PCT, and I L-6 in all measurement times were statistically different and sTREM- 1 did not yield statistical significance. A weak positive correlation was/bund between l L-6 in T 1 and T2 with the duration of the surgery （T 1 ： r= 0.4060, P 〈 0.0001 ; T2：r =0.3430, P〈0.0001）andOCT（T1：r= 0.3640, P〈0.0001,T2：r=0.3430, P〈0.0001）.AweakpositivecorrelationbetweenCRP in T2 and OCT （r = 0.4210, P 〈 0.0001 ） was also found. The interconnectivity of tested parameters showed a weak positive correlation between CRP and IL-6 in T1 （r= 0.3680; P 〈 0.0001 ）, moderate positive correlation in T2 （r = 0.6770; P 〈 0.0001）, and a strong positive correlation in T3 （r = 0.8651; P 〈 0.0001）. Conclusions： CRP, IL-6, and PCT were shown to be reliable for postoperative monitoring. Simultaneous determination of CRP and IL-6 might not be useful as they follow similar kinetics, sTREM- 1 might not be useful in CRC postoperative monitoring.

慢性阻塞性肺疾病合并呼吸衰竭患者行外周血TREM-1检测对序贯治疗切换点应用研究

目的:考察慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)合并呼吸衰竭患者行外周血髓样细胞触发受体-1(triggering receptor expressed on myeloid cells-1,TREM-1)检测对序贯治疗切换点应用研究。方法:收集120例COPD合并呼吸衰竭患者,随机分为对照组和观察组各60例。对照组接受2 h自主呼吸试验(spontaneous breathing trial,SBT)为无创序贯通气(non invasive positive pressure ventilation,NIPPV)选择时机,观察组接受外周血TREM-1≤90.0 pg/mL为NIPPV选择时机,检测两组患者机械通气治疗24 h后的应激激素、临床肺部感染评分和生命体征,记录两组的治疗时间和不良反应等。结果:两组的肾素(rennin,REN)、肾上腺素(Adrenaline,A)、去甲肾上腺素(noradrenaline,NA)和血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)比较,差异无统计学意义(P>0.05);与对照组比,观察组的临床肺部感染评分明显降低(P<0.05),两组患者的心率(heart rate,HR)、呼吸频率(respiratory rate,RR)、pH、动脉二氧化碳分压(arterial carbon dioxide partial pressure,PaCO 2)和动脉氧分压(partialpressureofoxygen,PaO 2)比较,差异无统计学意义(P>0.05),两组重症监护室(intensive care nursing,ICU)监护时间比较,差异无统计学意义(P>0.05);与对照组比,观察组有创通气时间、总机械通气时间和住院时间均明显降低(P<0.05),两组死亡、呼吸机相关性肺炎及再次插管发生比较,差异无统计学意义(P>0.05)。结论:COPD合并呼吸衰竭患者有创-无创序贯通气治疗期间以TREM-1作为切换点,有利于缩短患者创通气时间、总机械通气时间和住院时间。

Application of TREM-1 in peripheral blood as a switching point for sequential ventilation of patients with chronic obstructive pulmonary disease complicated with respiratory failure

Objective:To investigate the application of peripheral blood triggering receptor expressed on myeloid cells-1(TREM-1)for sequential treatment switching points in patients with chronic obstructive pulmonary disease(COPD)complicated with respiratory failure.Methods:A total of 120 cases of COPD patients with respiratory failure from June 2017 to December 2018 were randomly divided into two groups:60 cases in the control group and 60 cases in the observation group.The control group received spontaneous breathing trials for 2 h to select the time for non-invasive positive pressure ventilation,while the observation group received peripheral blood TREM-1(≤90.0 pg/mL)to select the time for non-invasive positive pressure ventilation.The stress hormones,clinical pulmonary infection score and vital signs of two groups after 24 h of mechanical ventilation were detected.The treatment time and the adverse reactions of the two groups were recorded.Results:There was no significant difference in rennin,adrenaline,noradrenaline and angiotensin II between two groups(P>0.05).Compared with the control group,the clinical pulmonary infection score was decreased in the observation group(P<0.05).There was no significant difference in heart rate,respiratory rate,pH,partial pressure of carbon dioxide and partial pressure of oxygen between two groups(P>0.05).There was no significant difference in intensive care monitoring time between two groups(P>0.05).Compared with the control group,the observation group had no significant difference in invasive ventilation time and total mechanical ventilation.The time of hospitalization and hospitalization had significantly decreased(P<0.05).There was no significant difference in mortality,ventilator-associated pneumonia and re-intubation between two groups(P>0.05).Conclusion:TREM-1 can be used as a switching point during invasive-noninvasive sequential ventilation for COPD patients with respiratory failure,which can shorten the time of invasive ventilation,total mechanical ventilation and hospitalization.