Home About us Contact
|
Home About us Contact | ||
|
|
||
Chemokine Induction (chemokine + induction)
Selected AbstractsAltered chemokine expression in the spinal cord and brain contributes to differential interleukin-1,-induced neutrophil recruitmentJOURNAL OF NEUROCHEMISTRY, Issue 2 2002Sandra J. Campbell Abstract The pattern of neutrophil recruitment that accompanies inflammation in the CNS depends on the site of injury and the stage of development. The adult brain parenchyma is refractory to neutrophil recruitment and associated damage as compared to the spinal cord or juvenile brain. Using quantitative Taqman RT,PCR and enzyme-liked immunosorbent assay (ELISA), we compared mRNA and protein expression of the rat neutrophil chemoattractant chemokines (CINC) in spinal cord and brain of adult and juvenile rats to identify possible association with the observed differences in neutrophil recruitment. Interleukin-1, (IL-1,) injection resulted in up-regulated chemokine expression in both brain and spinal cord. CINC-3 mRNA was elevated above CINC-1 and CINC-2,, with expression levels for each higher in spinal cord than in brain. By ELISA, IL-1, induced greater CINC-1 and CINC-2, expression compared to CINC-3, with higher protein levels in spinal cord than in brain. In the juvenile brain, significantly higher levels of CINC-2, protein were observed in response to IL-1, injection than in the adult brain following an equivalent challenge. Correspondingly, neutrophil recruitment was observed in the juvenile brain and adult spinal cord, but not in the adult brain. No expression of CINC-2, mRNA was detected. Thus differential chemokine induction may contribute to variations in neutrophil recruitment in during development and between the different CNS compartments. [source] Erythropoietin attenuates white matter damage, proinflammatory cytokine and chemokine induction in developing rat brain after intra-uterine infectionNEUROPATHOLOGY, Issue 5 2009Ying Shen To investigate the possible ameliorating effect of recombinant human erythropoietin (rhEPO) on white matter damage, pro-inflammatory cytokine and chemokine induction in developing rat brain after intra-uterine Escherichia coli infection. E. coli was inoculated into uterine cervix of the time-pregnant rats and the control was injected with normal saline. Following maternal E. coli inoculation, the pups received a single intraperitoneal injection of rhEPO at a dose of 5000 IU/kg body weight immediately after birth. Immunohistochemical staining and Western blot analysis for 2,, 3,-cyclic nucleotide 3,-phosphodiesterase (CNPase), neurofilament (NF) and glial fibrillary acidic protein (GFAP) were performed to assess white matter damage in pup brains at post-natal day 1 (P1), P3 and P7. Pro-inflammatory cytokines and chemokines were detected by real-time quantitative RT-PCR at the mRNA levels to evaluate the inflammatory response in pup brains at P1, P3 and P7. A single dose of rhEPO treatment (5000 IU/kg body weight) attenuated white matter damage in developing rat brain after intra-uterine E. coli infection. The protein levels of CNPase and NF in pup brains at P7 significantly increased after post-natal rhEPO treatment as compared with the intra-uterine E. coli -treated group. Also, post-natal rhEPO injection markedly attenuated the intra-uterine E. coli infection-induced increases in GFAP protein expression and the mRNA levels of pro-inflammatory cytokines and chemokines. Post-natal EPO administration as a single dose may exert a neuroprotective effect on white matter damage by reducing pro-inflammatory cytokine and chemokine induction in developing rat brain after intra-uterine E. coli infection. [source] Deficiency of CXCR2, but not other chemokine receptors, attenuates autoantibody-mediated arthritis in a murine modelARTHRITIS & RHEUMATISM, Issue 7 2010Jonathan P. Jacobs Objective Chemokines coordinate leukocyte trafficking in homeostasis and during immune responses. Prior studies of their role in arthritis have used animal models with both an initial adaptive immune response and an inflammatory effector phase. We undertook analysis of chemokines and their receptors in the effector phase of arthritis using the K/BxN mouse serum,transfer model. Methods A time-course microarray analysis of serum-transferred arthritis was performed, examining ankle tissue, synovial fluid, and peripheral blood leukocytes. Up-regulation of chemokines was confirmed by quantitative reverse transcriptase,polymerase chain reaction. The functional relevance of chemokine induction was assessed by transferring serum into mice deficient in CCR1,7, CCR9, CXCR2, CXCR3, CXCR5, CX3CR1, CCL2, or CCL3. Further mechanistic analysis of CXCR2 involved treatment of arthritic mice with a CXCR2 antagonist, bone marrow (BM) cell transfers with CXCR2+/, and CXCR2,/, donors and recipients, flow cytometry of synovial cells, and competition experiments measuring enrichment of CXCR2-expressing neutrophils in arthritic joints of mice with mixed CXCR2+/+ and CXCR2,/, BM cells. Results Gene expression profiling revealed up-regulation of the CXCR2 ligands CXCL1, CXCL2, and CXCL5 in the joint in parallel with disease activity. CXCR2,/, mice had attenuated disease relative to CXCR2+/, littermates, as did mice receiving the CXCR2 inhibitor, while deficiency of other chemokine receptors did not affect arthritis severity. CXCR2 was required only on hematopoietic cells and was widely expressed on synovial neutrophils. CXCR2-expressing neutrophils were preferentially recruited to arthritic joints in the presence of CXCR2-deficient neutrophils. Conclusion CXCR2 (but not other chemokine receptors) is critical for the development of autoantibody-mediated arthritis, exhibiting a cell-autonomous role in neutrophil recruitment to inflamed joints. [source] Chemokine expression in the white matter spinal cord precursor niche after force-defined spinal cord contusion injuries in adult ratsGLIA, Issue 8 2010Friederike Knerlich-Lukoschus Abstract Inflammatory cascades induced by spinal cord injuries (SCI) are localized in the white matter, a recognized neural stem- and progenitor-cell (NSPC) niche of the adult spinal cord. Chemokines, as integrators of these processes, might also be important determinants of this NSPC niche. CCL3/CCR1, CCL2/CCR2, and SDF-1,/CXCR4 were analyzed in the ventrolateral white matter after force defined thoracic SCI: Immunoreactivity (IR) density levels were measured 2 d, 7 d, 14 d, and 42 d on cervical (C 5), thoracic (T 5), and lumbar (L 5) levels. On day post operation (DPO) 42, chemokine inductions were further evaluated by real-time RT-PCR and Western blot analyses. Cellular phenotypes were confirmed by double labeling with markers for major cell types and NSPCs (nestin, Musashi-1, NG2, 3CB2, BLBP). Mitotic profiles were investigated in parallel by BrdU labeling. After lesion, chemokines were induced in the ventrolateral white matter on IR-, mRNA-, and protein-level. IR was generally more pronounced after severe lesions, with soaring increases of CCL2/CCR2 and continuous elevations of CCL3/CCR1. SDF-1, and CXCR4 IR induction was focused on thoracic levels. Chemokines/-receptors were co-expressed with astroglial, oligodendroglial markers, nestin, 3CB2 and BLBP by cells morphologically resembling radial glia on DPO 7 to DPO 42, and NG2 or Musashi-1 on DPO 2 and 7. In the white matter BrdU positive cells were significantly elevated after lesion compared with sham controls on all investigated time points peaking in the early time course on thoracic level: Here, chemokines were co-expressed by subsets of BrdU-labeled cells. These findings suggest an important role of chemokines/-receptors in the subpial white matter NSPC niche after SCI. © 2010 Wiley-Liss, Inc. [source] | |||||||||||||