Depressed CCL5 Expression in Human Pulmonary Tuberculosis

CCL5/regulated on activation, normal T expressed and secreted production (RANTES) is a principal CC chemokine, and can activate macrophages and Th1 lymphocytes, however, little is known about the CCL5 profiles associated with active tuberculosis (TB). In this study, we investigated the production of CCL5 by the peripheral blood mononuclear cells (PBMCs) of patients with active pulmonary TB after stimulation with Triton X-100 soluble proteins (TSP) or the 30-kDa antigen. The profiles of cytokines/chemokines [CXCL8/interleukin (IL)-8, IL-12 p40, and interferon (IFN)-gamma] were also examined by PBMCs from TB patients, and compared with those obtained from healthy tuberculin reactors (HTR). Concordant with earlier studies, IFN-gamma production was significantly depressed in the PBMCs from TB patients compared with those from HTR. In addition, the CCL5, but not CXCL8, levels in the PBMCs from TB patients were significantly depressed after stimulation for 18 hr compared to those in the PBMCs from HTRs. The CCL5 release was not significantly correlated with the release of IFN-gamma in the cells from TB patients and HTRs. Further, inhibitor studies show that the 30-kDa- or TSP-induced CCL5 mRNA expression is sensitive to inhibitors of mitogen-activated protein kinase kinase (MEK) 1/2 and Janus kinase (JAK) 2, but not p38, pathway activation, suggesting a MEK1/2- or JAK2-based mechanism is responsible for modulating of the CCL5 expression in human PBMCs. Collectively, these data suggest that TB patients show depressed production of CCL5 secretion, which can be modulated by MEK- and JAK2-based transcriptional regulatory mechanisms, in response to the mycobacterial antigens.

Human chorionic gonadotropin and invasion of trophoblast into the tubal wall in tubal pregnancy / 대한산부인과학회지

OBJECTIVE: To evaluate the relationship between gestational age, tubal ultrasonographic diameter, and serum beta-hCG levels and different stages of trophoblastic infiltration of the tubal wall in tubal pregnancy. METHODS: The 45 cases of fallopian tube containing tubal pregnancy were reviewed. Gestational age, diameter of the tubal mass, and beta-hCG level on the day of surgery were calculated by transvaginal sonography and immunoassay respectively. The tubal pregnancy was classified according to the depth of trophoblastic infiltration: trophoblast limited to the tubal mucosa (stage I), extension to the tubal muscularis (stage II), or complete tubal wall infiltration up to the serosa discontinued by trophoblastic cells (stage III). RESULTS: 14 patients (31.1%) had stage I tubal infiltration, 10 patients (22.2%) had stage II infiltration, 21 patients (46.7%) had stage III infiltration. There was no relationship between gestational age, tubal diameter and stage, but there was a predictable correlation between beta-hCG and the depth of trophoblastic invasion. The median beta-hCG level was 1,332.1 mIU/mL (range, 215-2,995 mIU/mL) for patients with stage I infiltration, 9,548.0 mIU/mL (range, 569-43,989 mIU/mL) for stage II infiltration, and 23,087.9 mIU/mL (range, 1,373-98,000 mIU/mL) for stage III infiltration. Cut off level of beta-hCG for each stage were 1,996.5 mIU/mL (stage I vs II, III) and 5,665 mIU/mL (stage I, II vs III) respectively. CONCLUSION: These findings may explain why beta-hCG is a important predicting factor for invasion of trophoblast in tubal pregnancy.