| Autor: |
Mohamed AF; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo, 11562, Egypt. ahmed.fathi@pharma.cu.edu.eg., El-Yamany MF; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo, 11562, Egypt., El-Batrawy FA; Department of Pharmacology, Faculty of Medicine, Cairo University, Cairo, Egypt., Abdel-Aziz MT; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo, 11562, Egypt. |
| Abstrakt: |
JNJ7777120, a histamine H4 receptor antagonist, was shown to be effective in different experimental settings of allergic inflammation, including contact hypersensitivity. Toll-like receptors (TLRs) are thought to function as a link between innate and adaptive immune responses to various haptens. Here, we studied the suppression of TLR signaling as a possible mechanism by which JNJ7777120 exerts its anti-inflammatory effects against the chemical hapten, fluorescein isothiocyanate (FITC). The potential anti-oxidant effect of JNJ7777120 in this model was also examined. Mice subjected to FITC sensitization and challenge showed significantly elevated plasma immunoglobulin E (IgE) level, ear interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid reactive substance (TBARS) contents as well as increased myeloid differentiation factor 88 (MyD88) gene expression, nuclear factor-kappa B p65 (NF-κB p65), and phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) protein expression. This was accompanied by enhanced ear myeloperoxidase (MPO) and eosinophil peroxidase (EPO) activities as well as diminished glutathione (GSH) content and superoxide dismutase (SOD) activity. JNJ7777120 treatment perceivably reversed these effects, denoting profound anti-inflammatory and anti-oxidant character of JNJ7777120 which was confirmed by its mitigation of FITC-induced pathological changes in mouse ear. JNJ7777120 additionally enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), providing a novel mechanism by which JNJ7777120 functions as an anti-oxidant in this model. To conclude, JNJ7777120 afforded a remarkable amendment of FITC skin insult by virtue of its anti-inflammatory and anti-oxidant effects; the mechanistic basis of these effects may include modulation of TLR and Nrf2 pathways. |
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