CXC Chemokine Receptor 4 Axis Research Articles

The Expression of Stromal Cell–derived Factor 1 (SDF-1) in Inflamed Human Dental Pulp

Although dental pulp progenitor/stem cells (DPSCs) are indispensable for repair after pulpal injury, the mechanisms regulating their recruitment and activation remain unknown. To address this issue, we evaluated whether DPSCs in inflamed dental pulp had an upregulation of the chemokine system, a system of proteins known to regulate cellular responses to inflammation. Stromal cell–derived factor 1 (SDF-1), a member of the CXC chemokine subfamily and its receptor CXC chemokine receptor 4 (CXCR4), were evaluated in inflamed dental pulps obtained from extracted human teeth that showed spontaneous pain and/or lingering pain in response to cold and/or heat stimulus and compared with control levels found in normal dental pulps obtained from healthy noncarious third molars. Using immunohistochemistry and real-time reverse-transcription polymerase chain reaction, the results indicated that in inflamed pulps the SDF-1/CXCR4 axis was mostly distributed in inflammatory cells and microvascular endothelial cells rather than in normal pulps. SDF-1 messenger RNA expression levels in clinically inflamed dental pulp were higher than those in healthy dental pulp. These findings suggest that SDF-1 plays an important role in the process of pulpal inflammation via the recruitment of CXCR4-expressing inflammatory cells, and the SDF-1/CXCR4 axis may be involved in the recruitment of dental pulp stem cells at the injury site.

The Expression and Role of Stromal Cell–derived Factor-1α–CXCR4 Axis in Human Dental Pulp

Recent reports have suggested that the stromal cell–derived factor (SDF)-1α–CXCR4 axis has a direct effect on stem and progenitor cell recruitment in muscle and neural tissue repair after injury. No information is available about SDF-1α or CXC chemokine receptor 4 (CXCR4) in dental tissues. The aim of this study was to assess the expression of SDF-1α and its receptor, CXCR4, in healthy or inflamed human dental pulp and to evaluate the effects of SDF-1α on dental pulp cells (DPCs) in both proliferation and migration in vitro. Immunohistochemical staining and reverse-transcription polymerase chain reaction detected weak expression of SDF-1α and CXCR4 in healthy dental pulp and strong expression of SDF-1α and CXCR4 in inflamed dental pulp. A methylthiazol tetrazolium assay showed that SDF-1α could not promote DPCs proliferation. A transmigration assay, however, indicated that SDF-1α enhanced DPCs migration, which could be abolished by anti-CXCR4 antibodies. Taken together, these results imply that the SDF-1α–CXCR4 axis may play a role in the recruitment of CXCR4-positive DPCs toward the damaged sites.

Relation between CXCR-4 expression, Flt3 mutations, and unfavorable prognosis of adult acute myeloid leukemia

AbstractRecently it was shown that, analogous to normal hematopoietic cells, the level of CXC chemokine receptor 4 (CXCR-4) expression on acute myeloid leukemia (AML) cells correlates with stromal cell derived factor-1 alpha (SDF-1)-induced chemotaxis. As we speculated that an anomalous organ distribution of AML cells could affect cell survival and thus result in an altered fraction surviving chemotherapy, we examined a possible correlation between patient prognosis and CXCR-4 expression in AML patients. We found that patients with a high CXCR-4 expression in the CD34+ subset had a significantly reduced survival and a higher probability of relapse, resulting in a median relapse-free survival (RFS) of only 8.3 months. CXCR-4 expression was significantly higher in fetal liver tyrosine kinase-3 (Flt3)/internal tandem duplication (ITD) AML than in Flt3/wild-type (wt) AML. Covariate analysis indicated that the prognostic significance of Flt3/ITDs with respect to RFS was no more apparent when analyzed in conjunction with the expression of CXCR-4 in the CD34+ subset, suggesting that the poor prognosis of Flt3/ITD AML might be subordinate to the increased CXCR-4 expression. Using a granulocyte colony-stimulating factor receptor (G-CSF-R)-expressing 32D cell line, we observed that SDF-1/CXCR-4 interaction is required for the survival of myeloid differentiating cells, and it also induces a block in G-CSF-induced myeloid differentiation. These data suggest that the SDF-1/CXCR-4 axis may influence therapy responsiveness and defines unfavorable prognosis in AML. (Blood. 2004;104:550-557)