DOI: 10.57760/sciencedb.j00217.05462
title: DEC2 deficiency promotes high incidence of cough after infection and the therapeutic mechanism of ephedrine hydrochloride
title: DEC2缺失促进感染后咳嗽高发及盐酸麻黄碱的治疗作用机制

description: Objective To explore the mechanism of DEC2 deficiency promoting high incidence of post infectious cough (PIC) after infection and the therapeutic effect of ephedrine hydrochloride (EH).Method PIC mouse model was established in C57BL/6 wild-type mice (WT) and DEC2 knockout mice (DEC2- KO) using smoke and LPS nasal drops, with or without treatment by EH. On day 12, 14, and 16 of PIC establishment, mice were induced to cough using capsaicin nebulization and counted the frequency of cough. Flow cytometry, RT-qPCR and Western blot (WB) technologies were used to detect changes in the local inflammatory microenvironment of the mouse lungs before or after modeling and treatment of EH, including IL-1, IL-6, IFN-γ and IL-1Ra, IL-6Ra, IFNGR1 receptors; The expression of NF-KB related signaling molecules (P65) was analyzed by RT-qPCR and WB in mouse lung tissues and CD45 negative primary pulmonary cells cultured with LPS or EH.Result The transcription of DEC2 was increased in PIC model mice, and the deficiency of DEC2 induced the cough frequency in DEC2-KO PIC mice 2-fold higher than WT PIC mice. The absence of DEC2 exacerbated LPS-induced pulmonary inflammatory response, especially increased expression of IL-1, IL-6, γ-interferon receptor (IFNGR), IL-1R, IL-6R in lung CD45- cells (P&lt;0.01), and activation of P65 was promoted (P&lt;0.01).After EH treatment, the cough frequency in DEC2-KO PIC mice was significantly reduced (P&lt;0.001), the expression of IL-1, IL-6, IFN-γ in lung and IL-1R, IL-6R, IFNGR in pulmonary CD45-cells were down-regulated (P&lt;0.01). The expression and activation of NF-kB induced by DEC2 deletion were significantly inhibited (P&lt;0.01).Conclusion The deficency of DEC2 can activate NFKB signal and promote the high expression of inflammatory cytokine and receptors in pulmonary CD45-cells, which is a risk factor in the high incidence of PIC. EH can inhibit the excessive-activation of NFkB signal and the inflammatory characteristics of lung local stromal cells caused by DEC2 absence, and that is the main part of pharmacological mechanism for effective treatment of EH targeting PIC.
description: Objective To explore the mechanism of DEC2 deficiency promoting high incidence of post infectious cough (PIC) after infection and the therapeutic effect of ephedrine hydrochloride (EH).Method PIC mouse model was established in C57BL/6 wild-type mice (WT) and DEC2 knockout mice (DEC2- KO) using smoke and LPS nasal drops, with or without treatment by EH. On day 12, 14, and 16 of PIC establishment, mice were induced to cough using capsaicin nebulization and counted the frequency of cough. Flow cytometry, RT-qPCR and Western blot (WB) technologies were used to detect changes in the local inflammatory microenvironment of the mouse lungs before or after modeling and treatment of EH, including IL-1, IL-6, IFN-γ and IL-1Ra, IL-6Ra, IFNGR1 receptors; The expression of NF-KB related signaling molecules (P65) was analyzed by RT-qPCR and WB in mouse lung tissues and CD45 negative primary pulmonary cells cultured with LPS or EH.Result The transcription of DEC2 was increased in PIC model mice, and the deficiency of DEC2 induced the cough frequency in DEC2-KO PIC mice 2-fold higher than WT PIC mice. The absence of DEC2 exacerbated LPS-induced pulmonary inflammatory response, especially increased expression of IL-1, IL-6, γ-interferon receptor (IFNGR), IL-1R, IL-6R in lung CD45- cells (P&lt;0.01), and activation of P65 was promoted (P&lt;0.01).After EH treatment, the cough frequency in DEC2-KO PIC mice was significantly reduced (P&lt;0.001), the expression of IL-1, IL-6, IFN-γ in lung and IL-1R, IL-6R, IFNGR in pulmonary CD45-cells were down-regulated (P&lt;0.01). The expression and activation of NF-kB induced by DEC2 deletion were significantly inhibited (P&lt;0.01).Conclusion The deficency of DEC2 can activate NFKB signal and promote the high expression of inflammatory cytokine and receptors in pulmonary CD45-cells, which is a risk factor in the high incidence of PIC. EH can inhibit the excessive-activation of NFkB signal and the inflammatory characteristics of lung local stromal cells caused by DEC2 absence, and that is the main part of pharmacological mechanism for effective treatment of EH targeting PIC.