Ghrelin Downregulates Lipopolysaccharide/ Leptin-Induced MUC5AC Expression in Human Nasal Epithelial Cells.

IF 2.9 3区医学 Q1 OTORHINOLARYNGOLOGY Clinical and Experimental Otorhinolaryngology Pub Date : 2023-02-01 DOI:10.21053/ceo.2022.00857

Yoon Seok Choi, Hyung Gyun Na, Chang Hoon Bae, Si-Youn Song, Yong-Dae Kim

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Abstract

Objectives: Obesity, which induces chronic low-grade systemic inflammation in the human body, is a known risk factor for various diseases. Recent studies have shown associations between various otorhinolaryngological diseases and obesity. In particular, inflammatory sinonasal diseases have been found to be strongly associated with obesity-related proinflammatory mediators. Many studies have been conducted to identify therapeutic agents for controlling obesity-related inflammatory airway diseases. Ghrelin, an endogenous peptide from the stomach, has anti-inflammatory and antioxidative effects in a wide range of tissues. However, the effect of ghrelin on the regulation of mucus secretion has not yet been studied in the human nasal mucosa. Therefore, we investigated the effects of ghrelin on lipopolysaccharide (LPS)/leptin-mediated MUC5AC expression and mechanisms involved in human nasal epithelial cells (HNEpCs).

Methods: In HNEpCs, the effect and signaling pathways of ghrelin on LPS/leptin-induced MUC5AC expression were examined using reverse transcription polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassays, Western blotting, and immunofluorescence staining.

Results: Growth hormone secretagogue receptor 1a (GHSR1a) was expressed in the HNEpCs. Ghrelin downregulated LPS/leptin-induced MUC5AC expression, which was abolished by D-Lys-3-growth hormone-releasing peptide 6 (D-Lys-3-GHRP-6). Ghrelin significantly inhibited LPS/leptin-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs). These ghrelin-mediated changes in MAPK activation were abolished by D-Lys-3-GHRP-6. These.

Results: showed that ghrelin inhibits LPS/leptin-induced MUC5AC overexpression by modulating the ERK1/2 and p38 MAPK pathways in HNEpCs.

Conclusion: These findings suggest that ghrelin is a potential therapeutic agent for treating obesity-related inflammatory sinonasal diseases.

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胃饥饿素下调脂多糖/瘦素诱导的人鼻上皮细胞MUC5AC表达

目的:肥胖可诱发人体慢性低度全身性炎症，是多种疾病的已知危险因素。最近的研究表明，各种耳鼻喉疾病与肥胖之间存在关联。特别是，炎症性鼻窦炎已被发现与肥胖相关的促炎介质密切相关。许多研究已经进行，以确定治疗药物控制肥胖相关的炎症性气道疾病。胃饥饿素是一种来自胃的内源性肽，在多种组织中具有抗炎和抗氧化作用。然而，胃饥饿素对人鼻黏膜粘液分泌的调节作用尚未被研究。因此，我们研究了胃饥饿素对脂多糖(LPS)/瘦素介导的MUC5AC表达的影响及其参与人鼻上皮细胞(HNEpCs)的机制。方法:采用逆转录聚合酶链反应、实时聚合酶链反应、酶免疫测定、Western blotting、免疫荧光染色等方法，检测ghrelin对LPS/leptin诱导的MUC5AC表达的影响及信号通路。结果:生长激素促分泌受体1a (GHSR1a)在HNEpCs中表达。Ghrelin下调LPS/ lepatin诱导的MUC5AC表达，而d - lys -3-生长激素释放肽6 (D-Lys-3-GHRP-6)可消除MUC5AC表达。Ghrelin显著抑制LPS/leptin激活的细胞外信号调节激酶1/2 (ERK1/2)和p38丝裂原激活蛋白激酶(MAPKs)。这些生长素介导的MAPK激活变化被D-Lys-3-GHRP-6所消除。这些。结果:ghrelin通过调节ERK1/2和p38 MAPK通路抑制LPS/leptin诱导的HNEpCs MUC5AC过表达。结论:胃饥饿素是治疗肥胖相关炎症性鼻窦疾病的潜在药物。

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来源期刊

Clinical and Experimental Otorhinolaryngology 医学-耳鼻喉科学

CiteScore

4.90

自引率

6.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical and Experimental Otorhinolaryngology (Clin Exp Otorhinolaryngol, CEO) is an international peer-reviewed journal on recent developments in diagnosis and treatment of otorhinolaryngology-head and neck surgery and dedicated to the advancement of patient care in ear, nose, throat, head, and neck disorders. This journal publishes original articles relating to both clinical and basic researches, reviews, and clinical trials, encompassing the whole topics of otorhinolaryngology-head and neck surgery. CEO was first issued in 2008 and this journal is published in English four times (the last day of February, May, August, and November) per year by the Korean Society of Otorhinolaryngology-Head and Neck Surgery. The Journal aims at publishing evidence-based, scientifically written articles from different disciplines of otorhinolaryngology field. The readership contains clinical/basic research into current practice in otorhinolaryngology, audiology, speech pathology, head and neck oncology, plastic and reconstructive surgery. The readers are otolaryngologists, head and neck surgeons and oncologists, audiologists, and speech pathologists.