Cellular neuroscienceExpression of interleukin-6 receptor α in normal and injured rat sciatic nerve
Section snippets
Teased nerve preparations
All procedures involving animals were carried out in accordance with the Institutional Guide for Ethical Animal Experimentation (National Autonomous University of Mexico), minimizing the number of animals used and their suffering. Male Wistar rats (250–350 g) were used in all experiments. Rats were killed by ether or CO2 overexposure. Crushed sciatic nerves, sympathetic trunk and sciatic nerve from normal adult rats were excised and desheathed. The nerves were split into manageable strands and
Immunoblot analysis of IL6-Rα in different tissues
Western blotting with anti-IL6-Rα of whole sciatic nerve, cerebral cortex, spleen, pancreas and liver revealed two bands of ∼80 kDa and ∼110 kDa (Fig. 1). The ∼80 kDa band corresponds to the glycosylated monomer of the mature form of IL6-Rα, while the ∼110-kDa band might correspond to a non-glycosylated dimer of IL6-Rα. All of the tissues we studied expressed IL6-Rα, but differences in the levels of expression were observed (Fig. 1).
Immunolocalization of IL6-Rα in the sciatic nerve
IL6-Rα expression was examined by immunohistochemistry in
Discussion
The cDNA of the human IL6-Rα encodes a protein of 468 amino acids. The mature form of IL6-Rα is a glycosylated 80 kDa form of the predicted 50 kDa precursor protein (Hirata et al 1989, Varghese et al 2002). By Western blot analysis the rabbit antiserum against the IL6-Rα recognizes two bands, one of ∼80 kDa corresponding to the mature glycosylated molecule and another one of ∼110 kDa, which might represent a dimer of the non-glycosylated precursor protein of 50 kDa. Both bands were observed in
Acknowledgments
We thank Prof. R. Mirsky and Dr. Bob Amess for critically reading and correcting the manuscript, Biol. Juan Carlos Rivera-Mulia for assistance with the figures and the deconvolution system, MVZ Claudia Rivera-Cerecedo for providing us with the rats used in this work. This work was supported by Conacyt-México, grant 33540-N and UAEMex grant 1977/2004 to M. A. R. Dent.
References (38)
- et al.
Quantification of interleukin-6 mRNA in Wallerian degeneration by competitive reverse transcription polymerase chain reaction
J Neuroimmunol
(1996) - et al.
Myelin synthesis in the peripheral nervous system
Prog Neurobiol
(2000) - et al.
Expression of interleukin-6 and its receptor in the sciatic nerve and cultured Schwann cells: relation to 18 kD fibroblast growth factor-2
Brain Res
(2000) - et al.
Induction of myelin gene expression in Schwann cell cultures by an interleukin-6 receptor-interleukin-6 chimera
FEBS Lett
(1999) - et al.
Myelination and myelin sheath remodeling in normal and pathological PNS nerve fibres
Prog Neurobiol
(1994) - et al.
Differential temporal expression of mRNAs for ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and their receptors (CNTFRa, LIFRb, IL6-Ra and gp130) in injured peripheral nerves
Brain Res
(1998) - et al.
Schwann cell development
- et al.
Proteomics of the injured rat sciatic nerve reveals protein expression dynamics during regeneration
Mol Cell Proteom
(2005) Wallerian degeneration: history and clinical significance
J Neurol Sci
(2004)- et al.
Up-regulation of leukaemia inhibitory factor and interleukin-6 in transected sciatic nerve and muscle following denervation
Neuromusc Disord
(1996)
Interleukin-6 and soluble interleukin-6 receptor: direct stimulation of gp130 and hematopoiesis
Blood
Activation of myelin genes during transdifferentiation from melanoma to glial cell phenotype
J Biol Chem
Three dimensional analysis of unmyelinated fibres in normal and pathological autonomic nerves
J Neuropathol Exp Neurol
Interleukin-6 attenuates the development of experimental diabetes-related neuropathy
Neuropathology
Postnatally induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects
J Exp Med
Regeneration of peripheral nervous system axons
Interleukin-6 production by Schwann cells and induction in sciatic nerve injury
J Neurochem
Linkage between axonal ensheathment and basal lamina production by Schwann cells
Annu Rev Neurosci
Schwann cell function depends upon axonal signals and basal lamina components
Ann N Y Acad Sci
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2013, International Review of NeurobiologyCitation Excerpt :Phosphorylated STAT3 dimers then translocate to the nucleus and initiate transcription of target genes (for review, see Eulenfeld et al., 2012). Proteins and mRNAs of IL-6, IL-6R, and IL-6’s signaling molecules are constitutively expressed at low levels in the structures of intact peripheral nerve but at higher levels in non-myelinating Schwann cells (Bolin, Verity, Silver, Shooter, & Abrams, 1995; Grothe et al., 2000; Kurek, Austin, Cheema, Bartlett, & Murphy, 1996; Lara-Ramirez, Segura-Anaya, Martinez-Gomez, & Dent, 2008). Schwann cells of the distal nerve stump constitute the main source of increased levels of IL-6 (Fig. 7.1F and G), its receptors, and signaling molecules.
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2011, Annals of AnatomyCitation Excerpt :Although the pathways are still not completely understood, all these results suggest that signalling for alterations of cytokines/chemokines in DRG is produced by WD. Cytokines/chemokines display pleiotropic effects mediated by corresponding receptors that are expressed in parallel in the distal nerve stump and DRG following nerve injury (Dubovy et al., 2010a,b; George et al., 2005; Lara-Ramirez et al., 2008; Schafers et al., 2008) and play a role in both axon regeneration and NPP induction (Abbadie et al., 2009; Temporin et al., 2008; Vogel et al., 2006). Further progress in acquiring knowledge of inflammatory reaction during WD and the effects of this reaction upon axon regeneration and NPP induction depends on proper use of nerve injury models while working under aseptic conditions.
inhibition of interleukin-6 attenuates erectile dysfunction in a rat model of nerve-sparing radical prostatectomy
2011, Journal of Sexual MedicineCitation Excerpt :Expression of IL‐6 mRNA after sciatic nerve injury has been observed in Schwann cells and vascular endothelial cells using in situ hybridization, demonstrating that IL‐6 is produced after nerve injury in Schwann cells around the site of injury [30]. Moreover, the expression of IL‐6R in the intact sciatic nerve has been observed in Schwann cells, and this expression increases with proximity to the crush lesion [30,31]. Both IL‐6 and IL‐6R were expressed after nerve injury in Schwann cells, which are glial cells in the peripheral nervous system.
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