title: Loss of SHP-1 phosphatase alters cytokine expression in the mouse hindbrain following cochlear ablation.
abstract: Inflammatory cytokines in the central nervous system are largely modulated by glial cells and influence neuronal responses to CNS injury. The protein tyrosine phosphatase SHP-1, an intracellular regulator of many cytokine signaling pathways, has been implicated in mediating the activation of glia. There is a direct correlation between abnormally activated microglia and neuron loss within the SHP-1 deficient motheaten (me/me) mouse auditory brainstem after afferent injury. In order to determine whether loss of SHP-1 creates an aberrant cytokine environment driving the abnormal activation of me/me microglia, the expression of interleukin-4 (IL-4), interleukin-10 (IL-10), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) was examined by enzyme-linked immunosorbent assay (ELISA). Normal uninjured me/me mice showed lower IL-10 but higher IL-1beta levels compared to wild-type. Following unilateral cochlear ablation, there is decreased expression of IL-4 and IL-10 in me/me brains compared to wild-type, but IL-1beta is significantly increased. These findings indicate that decreases in anti-inflammatory cytokines, in combination with increased expression of the pro-inflammatory cytokine IL-1beta, may initiate a robust inflammatory reaction within the me/me brain contributing to the neuronal degeneration in the deafferented me/me auditory brainstem. SHP-1 may therefore play a role in limiting CNS inflammation following injury and disease.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy and Allied Health Sciences, University of Montana, Missoula 59812, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Diana I
authors.initials: DI
authors.lastname: Lurie
mesh_terms: D000818:Animals; D003051:Cochlea / Q000601:surgery*; D016207:Cytokines / Q000235:genetics*; D007839:Functional Laterality; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009457:Neuroglia / Q000201:enzymology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000378:metabolism; D012249:Rhombencephalon / Q000201:enzymology* / Q000276:immunology
chemical_list: D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C509248:Ptpn6 protein, mouse