Inhibition of c-Fos expression attenuates IgE-mediated mast cell activation and allergic inflammation by counteracting an inhibitory AP1/Egr1/IL-4 axis

Abstract Background Activator protein-1 (AP1), a c-Fos–JUN transcription factor complex, mediates many cytobiological processes. c-Fos has been implicated in immunoglobulin (Ig)E activation of mast cells (MCs) via high-affinity IgE Fc receptor (Fc?RI) binding. This study examined involvement MC and tested the effects c-Fos/AP1 inhibitor T-5224 on MCs allergic responses. Methods In vitro studies were conducted with two model systems: rat basophilic leukemia (RBLs) mouse bone marrow derived (BMMCs). degranulation effector functions ?-hexosaminidase release cytokine secretion assays. was inhibited T-5224. activity suppressed short hairpin RNA targeting (shFos). vivo immune responses evaluated passive cutaneous anaphylaxis (PCA) ovalbumin-induced active systemic (ASA) models, as well an oxazolone (OXA)-induced atopic dermatitis, common disease. Results expression elevated transcriptionally translationally IgE-stimulated MCs. binding Egr1 (early growth response 1) promoter upregulated transcription, leading to production interleukin (IL)4. reduced Fc?RI-mediated (evidenced by histamine levels) diminished EGR1 IL4 expression. attenuated IgE-mediated PCA ASA it MC-mediated dermatitis mice. Conclusion can activate c-Fos/Egr1/IL-4 axis. suppresses thus represents promising potential strategy for treat diseases.