Stromal cell derived factor (SDF), expressing on bone marrow stromal cells is a CXC-type chemokine, which specifically chemoattracts hematopoietic stem cells (HSCs) expressing CXCR4. SDF plays important roles in homing and mobilizing of HSCs. In this paper the regulatory mechanism of SDF/CXCR4 in the HSC migration process is mainly reviewed.
Chemokine CXCL12 ; Chemokines, CXC ; physiology ; Hematopoietic Stem Cell Mobilization ; Humans ; Receptors, CXCR4 ; physiology ; Signal Transduction

With recent progress in stem cell-based research, there has been tremendous interest in stem cell-based tissue regeneration. Stem cells can be differentiated into specialized cells/tissues by growth factors and cytokines. These small molecules are thought to play an important role in both wound healing and tissue regeneration. However, their biological activity and signal transduction during tissue regeneration are poorly understood. With recent advances in signal transduction by growth factors, the receptor kinases and G protein-coupled receptors, an understanding in the underlying mechanism of how these factors regulate tissue regeneration beginning to take place. In this review, the potential underlying mechanisms of growth factor signaling in normal tissue regeneration and chronic wound healing is discussed. Thus, it is an aim to provide a basis for designing more specific therapies for tissue regeneration in the near future.
Animal ; Cell Physiology* ; Chemokines/physiology ; Chronic Disease ; Growth Substances/physiology ; Human ; Keloid/therapy ; Keloid/physiopathology ; Regeneration/physiology* ; Signal Transduction/physiology* ; Wound Healing/physiology

CKLF-like MARVEL transmembrane domain containing member/chemokine-like factor super family member (CKLFSF/CMTM) is a novel tumor suppressor gene. CMTM3 is broadly expressed in normal human tissues and evolutionary conserved,especially in testis,spleen,and some cells of peripheral blood mononuclear cells. However,its expression is undetectable or down-regulated in most carcinoma cell lines and tissues. Restoration of CMTM3 may inhibit the proliferation,migration,and invasion of carcinoma cells. Although the exact mechanism of its anti-tumor activity remains unclear,CKLFSF3/CMTM3 is closely connected with immune system and associated with sex during tumorigenesis. The study advances of CKLFSF3/CMTM3 are elaborated in this review as CMTM3 may be a new target in the gene therapies for tumors,especially genitourinary tumors,while further studies on CMTM3 and its anti-tumor mechanisms are warranted.
Cell Transformation, Neoplastic ; Chemokines ; genetics ; physiology ; Down-Regulation ; Humans ; Leukocytes, Mononuclear ; MARVEL Domain-Containing Proteins ; genetics ; physiology ; Male ; Neoplasms ; pathology

Human cytomegalovirus (HCMV) is an ubiquitous pathogen that infects a majority of the world's population. The virus can establish lifelong infection once the human body is infected by HCMV and virus can be reactivated from a latent state in immune suppressed individuals. HCMV has developed several strategies to evade host immune surveillance after millions of years of co-evolution with mankind. One of the classical tricks is encoding homologous to human immune factors or stealing host cellular genes that have significant functions in immune system. Virus encoded immune modulators which participate in regulating the major histocompatibility complex, cellular immunity, humoral immunity, cytokines and chemokines are supposed to play a significant role in the pathogenesis of HCMV. Evaluation of "mutually assured survival" relationship between virus and host provides important insights into viral immunopathogenesis and study of viral immunomodulatory proteins might help us to uncover new human genes that control immunity.
Animals ; Chemokines ; physiology ; Cytokines ; physiology ; Cytomegalovirus ; pathogenicity ; Cytomegalovirus Infections ; immunology ; Game Theory ; Humans ; Immunity, Humoral ; Killer Cells, Natural ; immunology

Prostate cancer (PCa) preferentially metastasizes to the bone marrow stroma of the axial skeleton. This activity is the principal cause of PCa morbidity and mortality. The exact mechanism of PCa metastasis is currently unknown, although considerable progress has been made in determining the key players in this process. In this review, we present the current understanding of the molecular processes driving PCa metastasis to the bone.
Bone Neoplasms ; physiopathology ; secondary ; Cell Adhesion ; physiology ; Cell Movement ; physiology ; Chemokines ; physiology ; Humans ; Lipids ; physiology ; Male ; Neoplasm Metastasis ; physiopathology ; Prostatic Neoplasms ; pathology ; physiopathology

CCL23 is a human CC chemokine with potential suppression effects on both human and murine myeloid progenitor cells both in vitro and in vivo, and only expressed and released by dendritic cells differentiated from monocytes in blood cells. However, recent study has shown that CCL23 was over-expressed in bone marrow and peripheral blood cells from pediatric patients with acute myeloid leukemia (AML). In order to investigate the effects of CCL23 on the development, therapy and prognosis of leukemia, the U937 cells, a leukemic cell strain, were adopted and cultured with rhCCL23 for 72 hours. The cell proliferation and apoptosis rate were detected by Cell Counting Kit-8 and FITC-AnnexinV/PI respectively; the morphologic changes and the expression of CCR1 (the only receptor of CCL23 known by now) were observed during the differentiation process. The results showed that no obvious effect on the proliferation, apoptosis and differentiation of U937 was found by using CCL23 alone (P > 0.05), but cultured in combination with CCL23 and PMA, the differentiation of U937 cells were promoted remarkably, during which the CCR1 expression increased (P < 0.05). It is concluded that CCL23 alone did not inhibit the proliferation and differentiation of U937, while its use in combination with PMA may possess synergistic effect on inducting differentiation of U937 through the increase of receptor CCR1 expression.
Apoptosis ; physiology ; Cell Proliferation ; drug effects ; Cell Transformation, Neoplastic ; drug effects ; Chemokines, CC ; pharmacology ; Humans ; U937 Cells

OBJECTIVE: To compare the differences of neutrophils chemotaxis ability in peritoneal cavity between normal rats and schizopherenic rats with cell dynamic visualization system. METHODS: In the study,18 healthy Kunming rats were randomly divided into 3 groups which were control group (n=6), 0.3 mg/kg MK-801 treatment group (n=6), 0.6 mg/kg dizocilpine maleate (MK-801) treatment group(n=6), extracted neutrophils separately, and observed the morphology and counted under a microscope. Each group of cells was divided into two parts for chemotactic experiment, called chemokine agent treatment group and no chemokine agent treatment group respectively, indicating control 1, 0.3 mg/kg MK-801 treatment 1,0.6 mg/kg MK-801 treatment 1 and control 2, 0.3 mg/kg MK-801 treatment 2,0.6 mg/kg MK-801 treatment 2. The dynamic migration of cells was recorded using the NIS-Elements software, and TAXIScan Analyzer 2 software was used to select 30 cells (n=30) in each group of cells and analyze cells migration trajectory, speed and distance, and use pair test and One-Way analysis of variance for statistical analysis. RESULTS: The number of neutrophils in control group, 0.3 mg/kg MK-801 treatment group and 0.6 mg/kg MK-801 treatment group were(1.00±0.03)×10⁴/mL,(0.05±0.02)×10⁴/mL,(0.32±0.01)×10⁴/mL respectively, the differences of results were statistically significant(P<0.05).Under the effect of chemotactic agent,the directional migration capability of neutrophils in control group 1, 0.3 mg/kg MK-801 treatment group 1 and 0.6 mg/kg MK-801 treatment group 1 were(0.85±0.11) radian,(1.00±0.11) radian,(0.96±0.10) radian respectively (P<0.05); the migration velocities of neutrophils were (0.09±0.02) μm/s,(0.12±0.01) μm/s,(0.14±0.01) μm/s respectively (P<0.05);the migration distances of neutrophils were (94.26±0.02) μm,(134.61±0.01) μm,(156.19±0.01) μm respectively(P<0.05). CONCLUSION Compared with neutrophils in peritoneal cavity of control group, the neutrophils in peritoneal cavity of schizophrenic rats have stronger chemotactic movement ability.
Animals ; Cell Movement ; Chemokines ; Chemotaxis ; Disease Models, Animal ; Dizocilpine Maleate ; Mice ; Neutrophils/physiology* ; Peritoneal Cavity ; Rats ; Schizophrenia/physiopathology*

Cell Adhesion Molecules ; physiology ; Chemokines ; physiology ; Cytokines ; physiology ; Genetic Predisposition to Disease ; Humans ; Lectins, C-Type ; physiology ; Peptidyl-Dipeptidase A ; physiology ; Receptors, Cell Surface ; physiology ; Severe Acute Respiratory Syndrome ; etiology ; genetics ; immunology

BACKGROUNDIn a previous study, we have verified that CXCR4 expression is correlated with tumor aggressive progression and poor prognosis in patients with epithelial ovarian cancer. The aim of this study was to explore the effect of CXCL12-CXCR4 axis on the metastasis of human ovarian cancer.

METHODSThe expressions of CXCR4 and CXCL12 mRNA and protein in human ovarian cancer cell line CAOV-3 was detected by RT-PCR and immunocytochemistry. Methythiazolyltetrazolium (MTT) was used to analyze the effect of different concentrations of CXCL12 on the proliferation of CAOV-3 cells. Transwell invasion chamber and matrigel were used to evaluate the effect of various concentrations of CXCL12 and ascites on the migration and invasion of CAOV-3 cells. The expressions of integrin beta(1) and vascular endothelial growth factor-C (VEGF-C) mRNA were detected by RT-PCR. Data were analyzed using ANOVA by SAS 6.12.

RESULTSUnder serum-free suboptimal culture conditions, CXCL12 (100 ng/ml) significantly enhanced the proliferation of CAOV-3 cells compared with the control and 10 ng/ml CXCL12 groups (0.428 +/- 0.051 vs. 0.325 +/- 0.045 and 0.328 +/- 0.039, P < 0.05). This enhancing effect of CXCL12 was significantly inhibited by 10 microg/ml neutralizing CXCR4 antibody or 1 microg/ml CXCR4 antagonist AMD3100. However, 10 microg/ml neutralizing CXCR4 antibody could not inhibit cell proliferation without CXCL12. The levels of migration and invasion of the CAOV-3 cells treated with 100 ng/ml CXCL12 were significantly higher than those in the control (migration: 523.3 +/- 25.2 vs 108.0 +/- 7.2; invasion: 39.3 +/- 4.0 vs. 4.0 +/- 1.0). The enhancing effect of CXCL12 on cell migration and invasion increased with the concentration of CXCL12 (100 ng/ml vs10 ng/ml: migration, 523.3 +/- 25.2 vs 211.7 +/- 24.7; invasion, 39.3 +/- 4.0 vs 15.7 +/- 3.1, P < 0.05), and was strongly inhibited by 10 microg/ml neutralizing CXCR4 antibody or 1 microg/ml AMD3100. The number of migrated and invading cells in the CAOV-3 added with ascites was significantly higher than those in the 100 ng/ml CXCL12 group (migration: 706.6 +/- 30.6 vs 523.3 +/- 25.2, invasion: 61.7 +/- 7.6 vs 39.3 +/- 4.0, P < 0.05). The level of integrin beta(1) mRNA was greatly increased at 3 hours after being treated with CXCL12 (0.53 +/- 0.10 vs. 1.53 +/- 0.16, P < 0.05), and VEGF-C mRNA displayed significant augment at 24 hours after being treated with CXCL12 (0.52 +/- 0.09 vs 1.11 +/- 0.15, P < 0.05).

CONCLUSIONSCXCL12 and its receptor CXCR4 can promote the proliferation, migration, invasion of ovarian cancer cell line CAOV-3 and enhance its secretion of integrin beta(1) and VEGF-C. These effects can be inhibited by neutralizing CXCR4 antibody or AMD3100. CXCL12-CXCR4 axis plays an important role in ovarian cancer growth and metastasis.

Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Chemokine CXCL12 ; Chemokines, CXC ; analysis ; physiology ; Female ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Ovarian Neoplasms ; pathology ; Receptors, CXCR4 ; analysis ; physiology

BACKGROUNDBioactive proteins, such as cytokines and chemokines, have not been systematically evaluated in healthy and preeclamptic pregnancies. We aimed to investigate the difference of these proteins between healthy and preeclamptic pregnancies in order to help clarify their potential roles in the pathogenesis of hypertension and proteinuria in preeclampsia.

METHODSSamples of amniotic fluid and maternal/umbilical cord blood were collected from normal pregnancies and women with preeclampsia for examination of bioactive proteins. Fifty-three pregnant women were enrolled in this study. Of them, 30 pregnant women were recruited as healthy controls, and 23 pregnant women were diagnosed with preeclampsia. An antibody array was used to screen for higher levels of cytokines and related proteins in amniotic fluid than in the blood samples, and these proteins were then selected for quantification by immunoassay.

RESULTSInterleukin-1 receptor 4, hepatocyte growth factor, and urokinase plasminogen activator receptor were significantly elevated in the blood of preeclampsia patients. In particular, interleukin-1 receptor 4 was 8-fold higher in preeclampsia patients than in the healthy pregnancies. Moreover, in cord blood samples hepatocyte growth factor and interleukin-8 were significantly higher in preeclampsia patients.

CONCLUSIONSBecause of the biologic activities, Interleukin-1 receptor 4, hepatocyte growth factor, urokinase plasminogen activator receptor and interleukin-8 in maternal and/or cord blood could play a role in the pathogenesis of hypertension and proteinuria in preeclampsia.

Adult ; Amniotic Fluid ; metabolism ; Chemokines ; analysis ; physiology ; Cytokines ; analysis ; physiology ; Female ; Humans ; Hypertension ; etiology ; L-Lactate Dehydrogenase ; blood ; Pre-Eclampsia ; metabolism ; Pregnancy ; Proteinuria ; etiology