Roles and mechanisms of circulating CEACAM1 in the cirrhosis-related intestinal hyperpermeability: in vitro approach.

BACKGROUND: Cirrhosis-related intestinal hyperpermeability and endotoxemia are characterized by intestinal epithelial cell apoptosis, impaired restitution (proliferation and migration), decreased tight junction protein levels, and subsequent barrier dysfunction. In addition to endotoxin and tumor necrosis factor-α (TNFα), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) plays crucial roles in the regulation of apoptosis, restitution, tight junction protein-maintained barrier function of intestinal epithelial cells. METHODS: This study aims to explore the roles and underlying mechanisms of CEACAM1 in cirrhosis-related intestinal hyperpermeability through in vitro approach. RESULTS: In cirrhotic patients, high serum levels of intestinal hyperpermeability (zonulin and endotoxin) markers were accompanied by elevated serum levels of TNFα and soluble CEACAM1. In in vitro experiments, we evaluated the individual and interacted roles of TNFα and human recombinant CEACAM1 (hrCEACAM1) in LC-sera (sera of cirrhotic patients)-induced intestinal hyperpermeability-related pathogenic signals. In the cell Line human from human colon (Caucasian colon adenocarcinoma) (Caco-2) cell culture, LC-sera, TNFα, and hrCEACAM1 increased apoptosis (measured by Terminal deoxynucleotidyl transferase [TdT] dUTP nick end labeling+/annexin-5+propidium iodide+ cells and caspase-3 activity), decreased restitution capacity (proliferation and migration), and disrupted tight junction protein-maintained barrier function in Caco-2 cells. The pathogenic changes mentioned above were accompanied by an increase in intracellular reactive oxygen species (ROS) levels, lactate dehydrogenase release, and endoplasmic reticulum stress-related signals in the LC-sera or TNFα-pretreated Caco-2 cells. Concomitant incubation of Caco-2 cells with anti-CEACAM1 suppressed these LC-sera or TNFα-induced negative effects on restitution, barrier function, and cell viability. CONCLUSION: This study demonstrated that sera from cirrhotic patients contain soluble CEACAM1, which is involved in the pathogenesis of intestinal hyperpermeability. Accordingly, it is noteworthy to explore the potential use of anti-CEACAM1 treatment for cirrhosis-related intestinal hyperpermeability and endotoxemia.

Expression of TSLC1 in patients with HAM/TSP.

Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic myelopathy characterized by slowly progressive spastic paraparesis and urinary dysfunction. A few biomarkers in the cerebrospinal fluid are known to be related to disease activity, but no biomarker has been reported in peripheral blood. This study aims to explore the expression level of the adhesion molecule during the expression level of the adhesion molecule among HAM/TSP disease activity. In lymphocyte function-associated antigen 1 and DNAX accessory molecule 1, no variation in expression levels specific to HTLV-1 infection was observed in CD4-positive T cells; however, TSLC1 expression was higher in HAM patients than in asymptomatic carriers and non-infected persons. TSLC1 tended to be higher in patients whose symptoms were worsening. On the contrary, the expression level of TSLC1 in CD8-positive T cells was lower in HAM patients than in asymptomatic carriers, and this tendency was stronger in patients whose symptoms had deteriorated. No significant correlation was found between TSLC1 and either of the transcription factors Tax or HBZ in any T cell group. Therefore, TSLC1 expression in CD4-positive T cells might be a useful biomarker of HAM/TSP disease activity.

Analysis of Swine Conventional Dendritic Cells, DEC205+CD172a+/-CADM1+, from Blood and Spleen in Response to PRRSV and PEDV.

Conventional dendritic cells (cDCs) cannot be infected by porcine reproductive and respiratory syndrome virus (PRRSV) but respond to infection via cytokine production, indicating a possible role in initiation/regulation of the immune response against PRRSV. In this work, we evaluated the responses of splenic and blood cDCs, with DEC205+CADM1+CD172a+/- phenotype, as well as those of CD163+ cells against PRRSV and porcine epidemic diarrhea virus (PEDV). Both populations were incubated in the presence of PRRSV or PEDV with and without naïve CD3+ T cells, and cytokine responses were evaluated by qPCR and ELISA. Our results showed that cDCs, but not CD163+ cells, produced IL-12 in response to PRRSV. PEDV did not induce IL-12 production. Cocultures of cDCs and autologous naïve CD3+ cells resulted in decreased IL-12 production and low expression of IFN-γ transcripts in response to PRRSV. Interestingly, cDCs increased the proliferation of naïve T cells in the presence of PRRSV compared with that achieved with monocytes and peripheral blood mononuclear cells (PBMCs). Cocultures of CD163+ cells induced IL-10 and IL-4 expression in the presence of PRRSV and PEDV, respectively. In conclusion, cDCs can selectively produce IL-12 in response to PRRSV but poorly participate in the activation of naïve T cells.

Plasma CADM1 promoter hypermethylation and D-dimer as novel metastasis predictors of cervical cancer.

AIM: Cervical cancer (CC) is the fourth malignant tumor in women worldwide. The metastasis is still the major reason for the treatment failures of most CC patients. Cell adhesion molecule 1 (CADM1) promoter methylation and plasma D-dimer levels have been reported to be increased in many types of cancers. The purpose of this study was to investigate the value of combinatorial assay of plasma CADM1 promoter hypermethylation and D-dimer as a metastasis marker in CC. METHODS: Two hundred and ninety-two patients with newly diagnosed cervical diseases and 70 healthy women were enrolled. A validation set comprised 36 Stage I CC patients and followed for 3 years. Plasma CADM1 promoter methylation and D-dimer levels were detected. RESULTS: The total coincidence rate of CADM1 promoter methylation status was 93.3% between 45 pair-matched tissue and plasma samples. Plasma CADM1 methylation levels in CC patients were higher than other benign disease groups (P = 0.000). Plasma CADM1 methylation levels had statistically differences between CC patients with and without lymph node metastasis (P = 0.049) or in CC patients with and without distant metastasis (P = 0.000). Similarly, plasma D-dimer levels in CC patients were higher than other benign disease groups (P < 0.05). D-dimer levels were only statistically different between CC patients with and without distant metastasis (P = 0.003). Combined assay of the two parameters for metastasis prediction has high sensitivity (80.4%) and specificity (90.5%). CONCLUSION: Combinatorial assay of plasma CADM1 methylation and D-dimer is a promising metastasis marker in cervical cancer.

The profiles of soluble adhesion molecules in the "great obstetrical syndromes".

OBJECTIVE: The objective of this study was to determine the profiles of maternal plasma soluble adhesion molecules in patients with preeclampsia, small-for-gestational-age (SGA) fetuses, acute pyelonephritis, preterm labor with intact membranes (PTL), preterm prelabor rupture of the membranes (preterm PROM), and fetal death. MATERIALS AND METHODS: A cross-sectional study was conducted to determine maternal plasma concentrations of sE-selectin, sL-selectin, and sP-selectin as well as sICAM-1, sVCAM-1, and sPECAM-1 in patients with (1) an uncomplicated pregnancy (control, n = 100); (2) preeclampsia (n = 94); (3) SGA fetuses (in women without preeclampsia/hypertension, n = 45); (4) acute pyelonephritis (n = 25); (5) PTL (n = 53); (6) preterm PROM (n = 24); and (7) fetal death (n = 34). Concentrations of soluble adhesion molecules and inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-8) were determined with sensitive and specific enzyme-linked immunoassays. RESULTS: In comparison to women with a normal pregnancy, (1) women with preeclampsia had higher median concentrations of sE-selectin, sP-selectin, and sVCAM-1, and a lower concentration of sL-selectin (all p values < .001); (2) patients with SGA fetuses had higher median concentrations of sE-selectin, sP-selectin, and sVCAM-1 (all p values < .05); (3) patients with a fetal death had higher median concentrations of sE-selectin and sP-selectin (all p values < .05); (4) patients with acute pyelonephritis had higher median plasma concentrations of sE-selectin, sICAM-1, and sVCAM-1 (all p values < .001); (5) patients with preeclampsia and acute pyelonephritis, plasma concentrations of sVCAM-1, sE-selectin, and sP-selectin correlated with those of the proinflammatory cytokines TNF-α and interleukin (IL)-8 (all p values < .05); (6) patients with PTL had a higher median concentration of sP-selectin and a lower median concentration of VCAM-1 (all p values < .05); and (7) women with preterm PROM had lower median concentrations of sL-selectin and sVCAM-1 (all p values < .05). CONCLUSIONS: The results of this study show that endothelial cell activation/dysfunction reflected by the plasma concentration of sE-selectin is not specific to preeclampsia but is present in pregnancies complicated by SGA fetuses, acute pyelonephritis, and fetal death. Collectively, we report that each obstetrical syndrome appears to have a stereotypical profile of soluble adhesion molecules in the peripheral circulation.