Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins

<p>Abstract</p> <p>Background</p> <p>In multiple sclerosis, inflammatory cells are found in both active and chronic lesions, and it is increasingly clear that cytokines are involved directly and indirectly in both formation and inhibition of lesions. We propose that cytokine mixtures typical of Th1 or Th2 lymphocytes, or monocyte/macrophages each induce unique molecular changes in glial cells.</p> <p>Methods</p> <p>To examine changes in gene expression that might occur in glial cells exposed to the secreted products of immune cells, we have used gene array analysis to assess the early effects of different cytokine mixtures on mixed CNS glia in culture. We compared the effects of cytokines typical of Th1 and Th2 lymphocytes and monocyte/macrophages (M/M) on CNS glia after 6 hours of treatment.</p> <p>Results</p> <p>In this paper we focus on changes with potential relevance for neuroprotection and axon/glial interactions. Each mixture of cytokines induced a unique pattern of changes in genes for neurotrophins, growth and maturation factors and related receptors; most notably an alternatively spliced form of trkC was markedly downregulated by Th1 and M/M cytokines, while Th2 cytokines upregulated BDNF. Genes for molecules of potential importance in axon/glial interactions, including cell adhesion molecules, connexins, and some molecules traditionally associated with neurons showed significant changes, while no genes for myelin-associated genes were regulated at this early time point. Unexpectedly, changes occurred in several genes for proteins initially associated with retina, cancer or bone development, and not previously reported in glial cells.</p> <p>Conclusion</p> <p>Each of the three cytokine mixtures induced specific changes in gene expression that could be altered by pharmacologic strategies to promote protection of the central nervous system.</p

Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for molecules associated with metabolism, signaling and regulation in central nervous system mixed glial cell cultures

<p>Abstract</p> <p>Background</p> <p>Cytokines secreted by immune cells and activated glia play central roles in both the pathogenesis of and protection from damage to the central nervous system (CNS) in multiple sclerosis (MS).</p> <p>Methods</p> <p>We have used gene array analysis to identify the initial direct effects of cytokines on CNS glia by comparing changes in early gene expression in CNS glial cultures treated for 6 hours with cytokines typical of those secreted by Th1 and Th2 lymphocytes and monocyte/macrophages (M/M).</p> <p>Results</p> <p>In two previous papers, we summarized effects of these cytokines on immune-related molecules, and on neural and glial related proteins, including neurotrophins, growth factors and structural proteins. In this paper, we present the effects of the cytokines on molecules involved in metabolism, signaling and regulatory mechanisms in CNS glia. Many of the changes in gene expression were similar to those seen in ischemic preconditioning and in early inflammatory lesions in experimental autoimmune encephalomyelitis (EAE), related to ion homeostasis, mitochondrial function, neurotransmission, vitamin D metabolism and a variety of transcription factors and signaling pathways. Among the most prominent changes, all three cytokine mixtures markedly downregulated the dopamine D3 receptor, while Th1 and Th2 cytokines downregulated neuropeptide Y receptor 5. An unexpected finding was the large number of changes related to lipid metabolism, including several suggesting a switch from diacylglycerol to phosphatidyl inositol mediated signaling pathways. Using QRT-PCR we validated the results for regulation of genes for iNOS, arginase and P glycoprotein/multi-drug resistance protein 1 (MDR1) seen at 6 hours with microarray.</p> <p>Conclusion</p> <p>Each of the three cytokine mixtures differentially regulated gene expression related to metabolism and signaling that may play roles in the pathogenesis of MS, most notably with regard to mitochondrial function and neurotransmitter signaling in glia.</p

Let them play: A prospective study of postoperative activity restrictions in children

Background: We aim to compare time to resume full activity, postoperative outcomes, and describe family preferences of self-directed activity restrictions (SDAR) and physician-directed activity restrictions (PDAR) following routine pediatric surgeries. Methods: We conducted a single institution, clinical trial (NCT04145895) from January 2020 to February 2022. Patients who presented for a routine inguinal hernia repair (ages 2-13) or laparoscopic appendectomy for uncomplicated appendicitis (aged ≤ 18) were eligible for participation. Participants chose to enroll in either the control (PDAR) or experimental (SDAR) groups. Control patients were instructed to restrict full activities for two weeks. For SDAR, patients were instructed to return to full activity when the patient and family felt comfortable doing so. Postoperatively, participants were asked to complete a survey to assess time to resume full activity, surgical complications, and patient and caregiver satisfaction. Results: 20 (24.4%) enrolled in PDAR and 62 patients (75.6%) enrolled in SDAR. The majority of patients underwent laparoscopic appendectomy (78%). Of patients who completed the postoperative survey, the average time to resume full activity was 11.91 days for PDAR and 9.51 days for SDAR (p = 0.328). There was no difference in parent satisfaction or postoperative complications (p >0.999). Conclusions: The time to resume full activity was two days sooner for SDAR without compromising post-operative outcomes. There are psychosocial benefits to children resuming normal activities, and SDAR may lessen a family's societal burden. Therefore, we propose that SDAR appears safe and should be utilized for routine surgery

Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins-1

<p><b>Copyright information:</b></p><p>Taken from "Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins"</p><p>http://www.jneuroinflammation.com/content/4/1/30</p><p>Journal of Neuroinflammation 2007;4():30-30.</p><p>Published online 18 Dec 2007</p><p>PMCID:PMC2228280.</p><p></p>e IgM and Cy 3-conjugated donkey anti-mouse IgG. Cultures were examined by indirect immunofluoresence as above. Compared to control, the Th1 treated A2B5+ oligodendrocyte precursors have a much more mature appearance including more extensive process formation although the cells still express A2B5, but do not express MHC class II

Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins-0

<p><b>Copyright information:</b></p><p>Taken from "Differential effects of Th1, monocyte/macrophage and Th2 cytokine mixtures on early gene expression for glial and neural-related molecules in central nervous system mixed glial cell cultures: neurotrophins, growth factors and structural proteins"</p><p>http://www.jneuroinflammation.com/content/4/1/30</p><p>Journal of Neuroinflammation 2007;4():30-30.</p><p>Published online 18 Dec 2007</p><p>PMCID:PMC2228280.</p><p></p>(IgG) followed by Alexa 488-conjugated goat anti-mouse IgM and Cy 3-conjugated donkey anti-mouse IgG. Cultures were examined for indirect immunofluoresence employing a Leitz Orthoplan 2 fluorescent microscope. The Th1 treated microglia (ED-1+ cells) have a different appearance when compared to those incubated with additional medium (control). Control microglia do not express MHC class II whereas Th1 treated microglia strongly express MHC class II molecules