Inhibition of tyrosine kinase signaling by tyrphostin AG126 downregulates the IL-21/IL-21R and JAK/STAT pathway in the BTBR mouse model of autism

Al-Ayadhi, 2005, Pro-inflammatory cytokines in autistic children in central Saudi Arabia, Neurosciences, 10, 155 Awasthi, 2007, A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells, Nat. Immunol., 8, 1380, 10.1038/ni1541 Adamson, 2009, The Current STAT us of lymphocyte signaling: new roles for old players, Curr. Opin. Immunol., 21, 161, 10.1016/j.coi.2009.03.013 Ashwood, 2011, Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome, Brain Behav. Immun., 25, 40, 10.1016/j.bbi.2010.08.003 Arrode-Brusés, 2012, Maternal immune activation by poly I:C induces expression of cytokines IL-1β and IL-13, chemokine MCP-1 and colony stimulating factor VEGF in fetal mouse brain, J. Neuroinflammation, 9, 83, 10.1186/1742-2094-9-83 American Psychiatric Association, 2013 Ahmad, 2016, The tyrosine kinase inhibitor tyrphostin AG126 reduces activation of inflammatory cells and increases Foxp3+ regulatory T cells during pathogenesis of rheumatoid arthritis, Mol. Immunol., 78, 65, 10.1016/j.molimm.2016.08.017 Ansari, 2016, Sinapic acid mitigates gentamicin-induced nephrotoxicity and associated oxidative/nitrosative stress, apoptosis, and inflammation in rats, Life Sci., 165, 1, 10.1016/j.lfs.2016.09.014 Ahmad, 2017, Imbalance between the anti- and pro-inflammatory milieu in blood leukocytes of autistic children, Mol. Immunol., 82, 57, 10.1016/j.molimm.2016.12.019 Ahmad, 2017, Dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in children with autism, Mol. Neurobiol., 54, 4390, 10.1007/s12035-016-9977-0 Ahmad, 2017, Upregulation of IL-9 and JAK-STAT signaling pathway in children with autism, Prog. Neuropsychopharmacol. Biol. Psychiatry, 79, 472, 10.1016/j.pnpbp.2017.08.002 Ahmad, 2017, Toll-like receptors, NF-κB, and IL-27 mediate adenosine A2A receptor signaling in BTBR T+ Itpr3tf/J mice, Prog. Neuropsychopharmacol. Biol. Psychiatry, 79, 184, 10.1016/j.pnpbp.2017.06.034 Ansari, 2017, Adenosine A2A receptor modulates neuroimmune function through Th17/retinoid-related orphan receptor gamma t (RORγt) signaling in a BTBR T+ Itpr3tf/J mouse model of autism, Cell. Signal., 36, 14, 10.1016/j.cellsig.2017.04.014 Ahmad, 2018, Protection by tyrosine kinase inhibitor, tyrphostin AG126, through the suppression of IL-17A, RORγt, and T-bet signaling, in the BTBR mouse model of autism, Brain Res. Bull., 142, 328, 10.1016/j.brainresbull.2018.08.020 Berg, 2005, Tec family kinases in T lymphocyte development and function, Annu. Rev. Immunol., 23, 549, 10.1146/annurev.immunol.22.012703.104743 Balachandra, 2005, Inhibition of tyrosine-kinase-mediated cellular signaling by tyrphostins AG 126 and AG556 modulates murine experimental acute pancreatitis, Surgery, 138, 913, 10.1016/j.surg.2005.05.021 Batten, 2006, Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells, Nat. Immunol., 7, 929, 10.1038/ni1375 Blanchard, 2012, BTBR Tþtf/J mice: autism-relevant behaviors and reduced fractone-associated heparan sulfate, Neurosci. Biobehav. Rev., 36, 2370, 10.1016/j.neubiorev.2012.09.005 Béchade, 2014, NOS2 expression is restricted to neurons in the healthy brain but is triggered in microglia upon inflammation, Glia, 62, 956, 10.1002/glia.22652 Bjorklund, 2016, Immune dysfunction and neuroinflammation in autism spectrum disorder, Acta Neurobiol. Exp. (Wars), 76, 257, 10.21307/ane-2017-025 Bakheet, 2017, Resveratrol ameliorates dysregulation of Th1, Th2, Th17, and T regulatory cell-related transcription factor signaling in a BTBR T+ tf/J mouse model of autism, Mol. Neurobiol., 54, 5201, 10.1007/s12035-016-0066-1 Cuzzocrea, 2000, The tyrosine kinase inhibitor tyrphostin AG126 reduces the development of acute and chronic inflammation, Am. J. Pathol., 157, 145, 10.1016/S0002-9440(10)64526-9 Chatterjee, 2003, The tyrosine kinase inhibitor tyrphostin AG126 reduces renal ischemia/reperfusion injury in the rat, Kidney Int., 64, 1605, 10.1046/j.1523-1755.2003.00254.x Chez, 2007, Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children, Pediatr. Neurol., 36, 361, 10.1016/j.pediatrneurol.2007.01.012 Clarkson, 2014, T cell-derived interleukin (IL)-21 promotes brain injury following stroke in mice, J. Exp. Med., 211, 595, 10.1084/jem.20131377 Careaga, 2015, Inflammatory profiles in the BTBR mouse: how relevant are they to autism spectrum disorders?, Brain Behav. Immun., 43, 11, 10.1016/j.bbi.2014.06.006 Chana, 2015, Decreased expression of mGluR5 within the dorsolateral prefrontal cortex in autism and increased microglial number in mGluR5 knockout mice: pathophysiological and neurobehavioral implications, Brain Behav. Immun., 49, 197, 10.1016/j.bbi.2015.05.009 Ernst, 2001, Effect of nicotine on brain activation during performance of a working memory task, Proc. Natl. Acad. Sci. U. S. A., 98, 4728, 10.1073/pnas.061369098 Enstrom, 2009, Altered gene expression and function of peripheral blood natural killer cells in children with autism, Brain Behav. Immun., 23, 124, 10.1016/j.bbi.2008.08.001 Eyerich, 2010, IL-17 and IL-22: siblings, not twins, Trends Immunol., 31, 354, 10.1016/j.it.2010.06.004 Gruys, 2005, Acute phase reaction and acute phase proteins, J. Zhejiang Univ. Sci. B, 6, 1045, 10.1631/jzus.2005.B1045 Genovese, 2007, S. Inhibition of tyrosine kinase-mediated cellular signalling by Tyrphostins AG126 and AG556 modulates secondary damage in experimental spinal cord trauma, Neuropharmacology, 52, 1454, 10.1016/j.neuropharm.2007.01.017 Goines, 2013, Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment, Neurotoxicol. Teratol., 36, 67, 10.1016/j.ntt.2012.07.006 Gottfried, 2015, The impact of neuroimmune alterations in autism spectrum disorder, Front. Psychiatry, 6, 121, 10.3389/fpsyt.2015.00121 Hanisch, 2001, The protein tyrosine kinase inhibitor AG126 prevents the massive microglial cytokine induction by pneumococcal cell walls, Eur. J. Immunol., 31, 2104, 10.1002/1521-4141(200107)31:7<2104::AID-IMMU2104>3.0.CO;2-3 Hsiao, 2012, Modeling an autism risk factor in mice leads to permanent immune dysregulation, Proc. Natl. Acad. Sci. U. S. A., 109, 12776, 10.1073/pnas.1202556109 Jyonouchi, 2001, Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression, J. Neuroimmunol., 120, 170, 10.1016/S0165-5728(01)00421-0 Jyonouchi, 2014, Cytokine profiles by peripheral blood monocytes are associated with changes in behavioral symptoms following immune insults in a subset of ASD subjects: an inflammatory subtype, Neuroinflammation, 27, 187, 10.1186/s12974-014-0187-2 Kann, 2004, The tyrosine kinase inhibitor AG126 restores receptor signaling and blocks release functions in activated microglia (brain macrophages) by preventing a chronic rise in the intracellular calcium level, J. Neurochem., 90, 513, 10.1111/j.1471-4159.2004.02534.x Kang, 2005, Inhibition of SRC tyrosine kinases suppresses activation of nuclear factor-kappaB, and serine and tyrosine phosphorylation of IkappaB-alpha in lipopolysaccharide-stimulated raw 264.7 macrophages, J. Toxicol. Environ. Health A, 68, 1643, 10.1080/15287390500192114 Kaur, 2005, Inducers of oxidative stress block ciliary neurotrophic factor activation of Jak/STAT signaling in neurons, J. Neurochem., 92, 1521, 10.1111/j.1471-4159.2004.02990.x Kebir, 2007, Human Th17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation, Nat. Med., 13, 1173, 10.1038/nm1651 Kazim, 2015, Sera from children with autism induce autistic features which can be rescued with a CNTF small peptide mimetic in rats, PLoS One, 10, 10.1371/journal.pone.0118627 Lowry, 1951, J. Biol. Chem., 193, 265, 10.1016/S0021-9258(19)52451-6 Liang, 2006, Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides, J. Exp. Med., 203, 2271, 10.1084/jem.20061308 Levillayer, 2007, Interleukin 22 is a candidate gene for Tmevp3, a locus controlling Theiler’s virus-induced neurological diseases, Genetics, 176, 1835, 10.1534/genetics.107.073536 Li, 2009, Elevated immune response in the brain of autistic patients, J. Neuroimmunol., 207, 111, 10.1016/j.jneuroim.2008.12.002 Mead, 2015, Evidence supporting an altered immune response in ASD, Immunol. Lett., 163, 49, 10.1016/j.imlet.2014.11.006 Marzocco, 2006, Tyrphostin AG 126 reduces intestinal ischemia-reperfusion injury in the rat, Naunyn Schmiedebergs Arch. Pharmacol., 372, 362, 10.1007/s00210-005-0029-y Mount, 2007, Involvement of interferon-gamma in microglial-mediated loss of dopaminergic neurons, J. Neurosci., 27, 3328, 10.1523/JNEUROSCI.5321-06.2007 Mostafa, 2010, Frequency of CD4+CD25high regulatory T cells in the peripheral blood of Egyptian children with autism, J. Child Neurol., 25, 328, 10.1177/0883073809339393 Menzfeld, 2015, Tyrphostin AG126 exerts neuroprotection in CNS inflammation by a dual mechanism, Glia, 63, 1083, 10.1002/glia.22803 Masi, 2017, The immune system, cytokines, and biomarkers in autism spectrum disorder, Neurosci. Bull., 33, 194, 10.1007/s12264-017-0103-8 Noriega, 2014, Immune dysregulation in autism spectrum disorder, Eur. J. Pediatr., 173, 33, 10.1007/s00431-013-2183-4 Nadeem, 2018, Activation of IL-17 receptor leads to increased oxidative inflammation in peripheral monocytes of autistic children, Brain Behav. Immun., 67, 335, 10.1016/j.bbi.2017.09.010 Onore, 2012, The role of immune dysfunction in the pathophysiology of autism, Brain Behav. Immun., 26, 383, 10.1016/j.bbi.2011.08.007 Shang-Jyh, 2005, Lipoteichoic acid induces nuclear factor-κB activation and nitric oxide synthase expression via phosphatidylinositol 3-kinase, Akt, and p38 MAPK in RAW 264.7 macrophages, Immunology, 115 Stumhofer, 2006, Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system, Nat. Immunol., 7, 937, 10.1038/ni1376 Tzartos, 2011, IL-21 and IL-21 receptor expression in lymphocytes and neurons in multiple sclerosis brain, Am. J. Pathol., 178, 794, 10.1016/j.ajpath.2010.10.043 Tomasik, 2016, Neuroimmune biomarkers in schizophrenia, Schizophr. Res., 176, 3, 10.1016/j.schres.2014.07.025 Widera, 2006, Tumor necrosis factor alpha triggers proliferation of adult neural stem cells via IKK/NF-kappaB signaling, BMC Neurosci., 7, 64, 10.1186/1471-2202-7-64 Whitney, 2009, Inflammation mediates varying effects in neurogenesis: relevance to the pathogenesis of brain injury and neurodegenerative disorders, J. Neurochem., 108, 1343, 10.1111/j.1471-4159.2009.05886.x Xu, 2013, IL-22 secreting CD4+ T cells in the patients with neuromyelitis optica and multiple sclerosis, J. Neuroimmunol., 261, 87, 10.1016/j.jneuroim.2013.04.021 Zimmerman, 2005, Cerebrospinal fluid and serum markers of inflammation in autism, Pediatr. Neurol., 35, 195, 10.1016/j.pediatrneurol.2005.03.014