Macrophages produce an array of proinflammatory mediators at sites of inflammation and contribute to the development of inflammatory responses. Important roles for cytokines, such as IL-1 or TNF-α, and bacterial products, such as LPS, in this process have been well documented; however, the role for the extracellular matrix proteins, such as collagen, remains unclear. We previously reported that discoidin domain receptor 1 (DDR1), a nonintegrin collagen receptor, is expressed during differentiation of human monocytes into macrophages, and the interaction of the DDR1b isoform with collagen facilitates their differentiation via the p38 mitogen-activated protein kinase (MAPK) pathway. In this study, we report that the interaction of DDR1b with collagen up-regulates the production of IL-8, macrophage inflammatory protein-1α, and monocyte chemoattractant protein-1 in human macrophages in a p38 MAPK- and NF-κB-dependent manner. p38 MAPK was critical for DDR1b-mediated, increased NF-κB trans-activity, but not for IκB degradation or NF-κB nuclear translocation, suggesting a role for p38 MAPK in the modification of NF-κB. DDR1b-mediated IκB degradation was mediated through the recruitment of the adaptor protein Shc to the LXNPXY motif of the receptor and the downstream TNFR-associated factor 6/NF-κB activator 1 signaling cascade. Taken together, our study has identified NF-κB as a novel target of DDR1b signaling and provided a novel mechanism by which tissue-infiltrating macrophages produce large amounts of chemokines during the development of inflammatory diseases. Intervention of DDR1b signaling may be useful to control inflammatory diseases in which these proteins play an important role.

Multidrug resistance (MDR) caused by overexpression of p-glycoprotein is a major obstacle in chemotherapy of malignant cancer, which usually is characterized by constitutive activation of signal transducer and activator of transcription 3 (STAT3), but their relation between MDR and STAT3 remains unclear. Here, we showed that STAT3 was overexpressed and highly activated in adriamycin-resistant K562/A02 cells compared with its parental K562 cells. Blockade of activation of STAT3 by STAT3 decoy oligodeoxynucleotide (ODN) promoted the accumulation and increased their sensitivity to adriamycin by down-regulating transcription of mdr1 and expression of P-gp, which were further confirmed by using STAT3-specific inhibitor JSI-124. Inhibition of STAT3 could also decrease mdr1 promoter mediated luciferase expression by using mdr1 promoter luciferase reporter construct. Otherwise, activation of STAT3 by STAT3C improved mdr1 transcription and P-gp expression. The ChIP results demonstrated that STAT3 could bind to the potential promoter region of mdr1, and STAT3 decoy depressed the binding. Further mutation assay show +64∼+72 region could be the STAT3 binding site. Our data demonstrate a role of STAT3 in regulation of mdr1 gene expression in myeloid leukemia and suggest that STAT3 may be a promising therapeutic target for overcoming MDR resistance in myeloid leukemia.

The improved R&R procedure in which medial rectus resection based on the near deviation with lateral rectus recession based on the distant deviation has a better alignment than the UMR and BMR surgeries for the treatment of children with CI-type IXT. All the UMR, BMR and improved R&R surgery can reduce near-distance differences in children with CI-type IXT.

PurposeTo assess the accuracy of the Plusoptix A09 photoscreener in detecting amblyopia risk factors in children and determine referral criteria when using Plusoptix A09 for a large-scale vision screening.MethodsPediatric patients attending our eye clinic underwent a comprehensive ophthalmic examination that included photorefraction, orthoptic examination, anterior segment assessment, fundus examination and cycloplegic retinoscopy. The measurements were collected for statistical analyses.ResultsOne hundred and seventy-eight children (mean age ± SD: 6.2±2.4 years, range: 2.2 to 14.1 years) were included in the study. The mean spherical equivalent (SE) obtained using Plusoptix A09 (PSE) was 0.57 D lower than that obtained from cycloplegic retinoscopy (CRSE) (P = 0.00). However, there was no statistically significant difference of Jackson cross cylinder J0 and J45 between Plusoptix A09 (PJ) and cycloplegic retinoscopy (CRJ) (P = 0.14, P = 0.26). The relationship of SE obtained from Plusoptix A09 and SE obtained from cycloplegic retinoscopy was presented as the equation: CRSE = 0.358 + 0.776 PSE + 0.064 PSE 2 + 0.011 PSE 3. Based on the Receiver Operating Characteristic (ROC) curve, the Plusoptix A09 had an overall sensitivity of 94.9% and specificity of 67.5% for detecting refractive amblyopia risk factors. The sensitivity and specificity of the Plusoptix A09 for detection of strabismus were 40.7% and 98.3%, respectively; detection of amblyopia and/or strabismus was 84.7% and 63.2%, respectively.ConclusionsThe Plusoptix A09 photoscreener underestimated hyperopia and overestimated myopia according to SE when compared with cycloplegic retinoscopy. The accuracy of the Plusoptix A09 in detecting amblyopia risk factors in children could be improved by the regression equation and optimized criteria for refractive amblyopia risk factors developed in the present study. Moreover, the Plusoptix A09 photoscreener is not suitable for a large-scale strabismus screening when it is applied solely.