Relationship between CCL21 and TREM2/DAP12 signaling pathways in spinal dorsal horn in remifentanil-induced hyperalgesia in mice with incisional pain / 中华麻醉学杂志

Objective:To evaluate the relationship between CCL21 and triggering receptor expressed on myeloid cells 2 (TREM2)/DNAX-activating protein of 12 kDa (DAP12) signaling pathways in the spinal dorsal horn in remifentanil-induced hyperalgesia in mice with incisional pain.Methods:Thirty-two SPF healthy male C57BL/6J mice, weighing 18-22 g, aged 8-10 weeks, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), CCL21 neutralizing antibody group (group anti-CCL21), remifentanil + incisional pain group (group R+ I), and CCL21 neutralizing antibody + remifentanil + incisional pain group (group anti-CCL21+ R+ I).A CCL21 neutralizing antibody 0.3 μg (diluted to 10 μl in normal saline) was intrathecally injected in anti-CCL21 and anti-CCL21+ R+ I groups twice a day.Normal saline 10 μl was intrathecally injected at the same time point twice a day in C and R+ I groups.Fifteen min after intrathecal injection, normal saline 0.1 ml was injected via the caudal vein for 4 consecutive times at an interval of 15 min in C and anti-CCL21 groups, and remifentanil 10 μg/kg (diluted to 0.1 ml in normal saline) was injected via the caudal vein for 4 consecutive times at an interval of 15 min in R+ I and anti-CCL21+ R+ I groups.The tail-flick latency (TFL) and mechanical paw withdrawal threshold (MWT) were measured at 24 h before remifentanil or normal saline injection (T 0) and 3, 6, 24 and 48 h after stopping injection of remifentanil or normal saline (T 1-4).The mice were sacrificed after the last measurement of pain threshold, and L 4-6 segments of the spinal cord were removed for determination of the expression of TREM2 and DAP12 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction). Results:Compared with group C, TFL was significantly shortened and MWT was decreased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was up-regulated in group R+ I and R+ I+ anti-CCL21 ( P<0.05), and no significant change was found in the parameters mentioned above in group anti-CCL21 ( P>0.05).Compared with group R+ I, TFL was significantly prolonged and MWT was increased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was down-regulated in group anti-CCL21+ R+ I ( P<0.05). Conclusions:CCL21 is involved in remifentanil-induced hyperalgesia by activating TREM2/DAP12 signaling pathways in the spinal dorsal horn of mice with incisional pain.

Clinical prediction value of chemokine CCL21 level for acute coronary syndrome / 中华老年医学杂志

Objective To investigate the clinical prediction value of chemokine CCL21 level for acute coronary syndrome.Methods Totally 212 patients receiving coronary arteriography were divided into acute myocardial infarction group(AMI,n=72),unstable angina pectoris group(UAP,n=76),and stable angina pectoris group(SAP,n=64).The serum level of chemokine CCL21 was detected by double-antibody sandwich enzyme-linked immunosorbent assay (ELISA)and the pathological changes of coronary artery were measured by Gensini scoring system.All patients were followed up for six months and the cardiovascular adverse events were recorded.Results The serum level of CCL21 was(169.72±14.64)ng/L in AMI group,(154.42±16.50)ng/L in UAP group,and(143.87±9.80) ng/L in SAP group,with statistically significant differences (F =99.818,P =0.000).Serum levels of CCL21 in ACS group and SAP group were positively correlated with Gensini score(r=0.474,P =0.000;r=0.350,P=0.049).Binary Logistic regression analysis revealed that chemokine CCL21 was an independent risk factor for predicting acute coronary syndrome (OR =1.049,P =0.022).The CCL21-judged area under the ROC curve in acute coronary syndrome group was 0.887 ± 0.028 (P =0.000),with diagnostic point of serum level of chemokine CCL21 at 159.15 ng/L,sensitivity of 0.635,specificity of 0.981.Serum level of CCL21 was higher in the patients with cardiovascular adverse events than in the patients without cardiovascular adverse events[(168.57±7.24)ng/L vs.(156.92± 6.53) ng/L],with statistically significant difference (t =16.100,P =0.000).Conclusions Serum level of chemokine CCL21 reflects the severity degree of coronary artery disease.The chemokine CCL21,as an independent and effective marker,can predict acute coronary syndrome.

Role of cemokine ligand 21 in spinal cord in tibia bone cancer pain in rats / 中华麻醉学杂志

Objective To investigate the role of chemokine ligand 21 (CCL21) in the spinal cord in tibia bone cancer pain (BCP) in rats.Methods Forty adult female SD rats weighing 160-180 g were randomly divided into 5 groups (n=8 each):sham operation group (group Ⅰ ); sham operation + CCL21 neutralizing antibody group (groupⅡ); BCP group (group [); BCP + PBS group (group Ⅳ); BCP + control IgG group (groupⅤ)and BCP + CCL21 neutralizing antibody group (group Ⅵ).BCP was induced by inoculating Walker-256 mammary gland carcinoma cells into the rat tibia medullary cavity in groups Ⅲ-Ⅵ.PBS 15 μl,IgG 10 μg and CCL21 neutralizing antibody 10 μg were injected intrathecally (IT) at 14 days after intra-tibial injection of Walker-256 mammary gland cancer cells in groups Ⅳ- Ⅵ respectively.Mechanical withdrawal threshold to yon Frey filament stimulation (MWT) was measured at 1 day before (To,baseline) ; 7 and 14 d after Walker-256 cell injection (T1,T2)and at 0.5,1,2,4,8,12,24 and 48 h after intrathecal injection (T3-10 ).Results Intra-tibial injection of Walker-256 mammary gland cancer cells significantly decreased MWT as compared with the baseline values in administration of CCL21 neutralizing antibody at T5-8 as compared with MWT before intrathecal administration at T2 in group Ⅵ.MWT was significantly lower in groups Ⅲ- Ⅳ than in groups Ⅰ and Ⅱ.MWT was significantly higher at T5-8 in group Ⅵ than in groups Ⅲ - Ⅴ.Conclu]sion CCL21 in the spinal cord is involved in the maintenance of tibia BCP in rats.

CCL21/CCR7 axis and mechanisms of tumor invasion and metastasis / 国际肿瘤学杂志

Secondary lymphoid tissue chemokine (CCL21) is a double-edged sword, which exerts antitumor, anti-infection immune response by binding to the receptor CCR7 on the surface of the multiple immune cells. However, a variety of tumor cells also express the receptor CCR7, the combination of CCL21 with CCR7promotes the invasion and metastasis of tumor cells, leading to the facilitation of tumor development. Therefore,exploring the mechanism(s) of tumor invasion and metastasis might be helpful for use of CCL21 as tumor gene therapy through blocking of CCL21's promotion of tumor invasion and metastasis.