Ciliary neurotrophic factor and interleukin-6 differentially activate microglia

Journal of Neuroscience Research
J Kyle KradySteven W Levison

Abstract

Studies have shown that cytokines released following CNS injury can affect the supportive or cytotoxic functions of microglia. Interleukin-6 (IL-6)-family cytokines are among the injury factors released. To understand how microglia respond to IL-6 family cytokines, we examined the effects of ciliary neurotrophic factor (CNTF) and IL-6 on primary cultures of rat microglia. To assess the functional state of the cells, we assayed the expression of tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and cyclooxygenase 2 (COX-2) following stimulation. We show that CNTF reduces COX-2 levels, whereas IL-6 increases the expression of IL-1beta, TNFalpha, and Cox-2. We also examined trophic factor expression and found that CNTF enhances glial cell-line derived neurotrophic factor (GDNF) mRNA and protein secretion, whereas IL-6 has no effect. Correspondingly, conditioned media from CNTF-stimulated microglia promote motor neuron survival threefold beyond controls, whereas IL-6-stimulated microglia decrease neuronal survival twofold. To understand better the signaling mechanisms responsible for the opposite responses of these IL-6-family cytokines, we examined STAT-3 and ERK phosphorylation in CNTF- and IL-6-stimulated mic...Continue Reading

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Citations

Aug 13, 2009·Developmental Neuroscience·Zinaida S Vexler, Midori A Yenari
Dec 6, 2012·Translational Neurodegeneration·Xiao-Guang Luo, Sheng-Di Chen
Jan 18, 2011·Brain Research Reviews·Anneleen SpoorenSarah Gerlo
Feb 4, 2010·Pharmacology & Therapeutics·Anneke Van der WaltTrevor Kilpatrick
Nov 6, 2012·Progress in Neuro-psychopharmacology & Biological Psychiatry·Kyoung-Sae NaYong-Ku Kim
Sep 29, 2017·International Journal of Molecular Sciences·Raili Riikonen
Apr 11, 2008·Neurochemical Research·Tsung-I LeeShun-Fen Tzeng
Aug 10, 2017·Journal of Neuropathology and Experimental Neurology·Malgorzata Ziemka-NaleczTeresa Zalewska
May 19, 2019·Cancers·Brennan Olson, Daniel L. Marks
Jun 27, 2019·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Benjamin B TournierPhilippe Millet
Jan 9, 2021·Journal of Neuroscience Research·Rongjiao ShaoDerong Cui
Jan 24, 2021·Journal of Neuroinflammation·Mireia RecasensBernardo Castellano
Aug 28, 2021·Cancers·Brennan OlsonDaniel L Marks

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