Role of histamine H4 receptor in the anti-inflammatory pathway of glucocorticoid-induced leucin zipper (GILZ) in a model of lung fibrosis

被引：0

作者：

Sgambellone, Silvia ^{[1
]}

Febo, Marta ^{[2
]}

Durante, Mariaconcetta ^{[1
]}

Marri, Silvia ^{[1
]}

Villano, Serafina ^{[1
]}

Bereshchenko, Oxana ^{[3
]}

Migliorati, Graziella ^{[2
]}

Masini, Emanuela ^{[1
]}

Riccardi, Carlo ^{[2
]}

Bruscoli, Stefano ^{[2
]}

Lucarini, Laura ^{[1
]}

机构：

[1] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEUROF, Sect Pharmacol, Viale Gaetano Pieraccini 6, I-50139 Florence, Italy

[2] Univ Perugia, Dept Med & Surg, Sect Pharmacol, Piazzale Severi 1, I-06132 Perugia, Italy

[3] Univ Perugia, Dept Philosophy Social Sci & Educ, I-06100 Perugia, Italy

来源：

INFLAMMATION RESEARCH | 2023年 / 72卷 / 10-11期

关键词：

Pulmonary fibrosis; Glucocorticoids; GILZ; Histaminergic system; Inflammation; IDIOPATHIC PULMONARY-FIBROSIS; AIRWAY INFLAMMATION; T-LYMPHOCYTES; INHIBITION; MICE; DIFFERENTIATION; ACTIVATION; PREVENTION; HYDAMTIQ; UPDATE;

D O I：

10.1007/s00011-023-01802-3

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

IntroductionThis study investigates the interactions between histaminergic system and glucocorticoid-induced leucin zipper (GILZ) in the inflammatory process and glucocorticoid modulation in lung fibrosis.MethodsWild-type (WT) and GILZ Knock-Out (KO) mice were treated with bleomycin (0.05 IU) or saline, delivered by intra-tracheal injection. After surgery, mice received a continuous infusion of JNJ7777120 (JNJ, 2 mg/kg b.wt.) or vehicle for 21 days. Lung function was studied by measuring airway resistance to air insufflation through the analysis of pressure at airway opening (PAO). Lung samples were collected to evaluate the expression of histamine H4R, Anx-A1, and p65-NF-kB, the activity of myeloperoxidase (MPO), and the production of pro-inflammatory cytokines.ResultsAirway fibrosis and remodeling were assessed by measuring TGF-beta production and alpha-SMA deposition. JNJ reduces PAO in WT but not in GILZ KO mice (from 22 +/- 1 mm to 15 +/- 0.5 and from 24 +/- 1.5 to 19 +/- 0.5 respectively), MPO activity (from 204 +/- 3.13 pmol/mg to 73.88 +/- 2.63 in WT and from 221 +/- 4.46 pmol/mg to 107 +/- 5.54 in GILZ KO), the inflammatory response, TGF-beta production, and alpha-SMA deposition in comparison to WT and GILZ KO vehicle groups.ConclusionIn conclusion, the role of H4R and GILZ in relation to glucocorticoids could pave the way for innovative therapies to counteract pulmonary fibrosis.

引用

页码：2037 / 2052

页数：16