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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 2018; 142:328-337BR

Abstract

Autism spectrum disorder (ASD) is an extremely predominant neurodevelopmental disorder expressed as impairment in reciprocal social interaction along with repetitive, restricted, and stereotyped behaviors. The protein tyrosine kinase inhibitor, tyrphostin AG126 (AG126), regulates the expression of several genes that play an important role in the development of neuroinflammatory disorders. Here, we investigate the possible effects of AG126 (5 mg/kg daily through intraperitoneal injection) on self-grooming, marble burying, and hot plate test results in BTBR T + Itpr3tf/J mice (BTBR is a model of autism). We also explore the effects of AG126 administration on IL-17 A, RORγt, T-bet, and IFN-γ production in CD4+ T cells and on CCR6+ chemokine receptors in splenic cells. We further investigated the effect of AG126 administration on the mRNA and protein expression of IL-17 A, RORγt, T-bet, IFN-γ, and NF-κB in the brain tissue. Our results demonstrate that treatment of BTBR mice with AG126 reduced repetitive self-grooming scores and lowered hot plate sensitivity potentials. Furthermore, AG126 administration also caused a substantial reduction of IL-17 A, RORγt, T-bet, and IFN-γ production in CD4+ T cells and on CCR6+ chemokine receptors in splenic cells. BTBR mice treated with AG126 also show decreased mRNA and protein expression levels of IL-17 A, RORγt, T-bet, IFN-γ, and NF-κB activation in brain tissue. Our results indicate that treating BTBR mice with AG126 leads to protection against neuroimmune dysfunction/dysregulation through the inhibition of cytokines and transcription factor signaling. This mechanism may be useful in the development of future therapies for neuroimmune disorders.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Electronic address: fashaikh@ksu.edu.sa.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Cairo, Egypt.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30172736

Citation

Ahmad, Sheikh F., et al. "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 Research Bulletin, vol. 142, 2018, pp. 328-337.
Ahmad SF, Ansari MA, Nadeem A, et al. 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. 2018;142:328-337.
Ahmad, S. F., Ansari, M. A., Nadeem, A., Bakheet, S. A., Alshammari, M. A., & Attia, S. M. (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 Research Bulletin, 142, pp. 328-337. doi:10.1016/j.brainresbull.2018.08.020.
Ahmad SF, et al. 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. 2018;142:328-337. PubMed PMID: 30172736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Ahmad,Sheikh F, AU - Ansari,Mushtaq A, AU - Nadeem,Ahmed, AU - Bakheet,Saleh A, AU - Alshammari,Musaad A, AU - Attia,Sabry M, Y1 - 2018/08/30/ PY - 2018/02/20/received PY - 2018/08/16/revised PY - 2018/08/27/accepted PY - 2018/9/3/pubmed PY - 2019/7/31/medline PY - 2018/9/3/entrez KW - Autism KW - BTBR T(+) Itpr3tf/J mice KW - IL-17/RORγt KW - Spleen cells brain tissue KW - Tyrosine kinase inhibitor AG126 SP - 328 EP - 337 JF - Brain research bulletin JO - Brain Res. Bull. VL - 142 N2 - Autism spectrum disorder (ASD) is an extremely predominant neurodevelopmental disorder expressed as impairment in reciprocal social interaction along with repetitive, restricted, and stereotyped behaviors. The protein tyrosine kinase inhibitor, tyrphostin AG126 (AG126), regulates the expression of several genes that play an important role in the development of neuroinflammatory disorders. Here, we investigate the possible effects of AG126 (5 mg/kg daily through intraperitoneal injection) on self-grooming, marble burying, and hot plate test results in BTBR T + Itpr3tf/J mice (BTBR is a model of autism). We also explore the effects of AG126 administration on IL-17 A, RORγt, T-bet, and IFN-γ production in CD4+ T cells and on CCR6+ chemokine receptors in splenic cells. We further investigated the effect of AG126 administration on the mRNA and protein expression of IL-17 A, RORγt, T-bet, IFN-γ, and NF-κB in the brain tissue. Our results demonstrate that treatment of BTBR mice with AG126 reduced repetitive self-grooming scores and lowered hot plate sensitivity potentials. Furthermore, AG126 administration also caused a substantial reduction of IL-17 A, RORγt, T-bet, and IFN-γ production in CD4+ T cells and on CCR6+ chemokine receptors in splenic cells. BTBR mice treated with AG126 also show decreased mRNA and protein expression levels of IL-17 A, RORγt, T-bet, IFN-γ, and NF-κB activation in brain tissue. Our results indicate that treating BTBR mice with AG126 leads to protection against neuroimmune dysfunction/dysregulation through the inhibition of cytokines and transcription factor signaling. This mechanism may be useful in the development of future therapies for neuroimmune disorders. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/30172736/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(18)30115-1 DB - PRIME DP - Unbound Medicine ER -