Ghrelin Downregulates Lipopolysaccharide/ Leptin-Induced MUC5AC Expression in Human Nasal Epithelial Cells
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Objectives. Obesity, which induces chronic low-grade systemic inflammation in the human body, is a known risk factor forvarious diseases. Recent studies have shown associations between various otorhinolaryngological diseases and obesi-ty. In particular, inflammatory sinonasal diseases have been found to be strongly associated with obesity-related pro-inflammatory mediators. Many studies have been conducted to identify therapeutic agents for controlling obesity-re-lated inflammatory airway diseases. Ghrelin, an endogenous peptide from the stomach, has anti-inflammatory andantioxidative effects in a wide range of tissues. However, the effect of ghrelin on the regulation of mucus secretionhas not yet been studied in the human nasal mucosa. Therefore, we investigated the effects of ghrelin on lipopolysac-charide (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 ex-amined using reverse transcription polymerase chain reaction, real-time polymerase chain reaction, enzyme immu-noassays, Western blotting, and immunofluorescence staining. Results. Growth hormone secretagogue receptor 1a (GHSR1a) was expressed in the HNEpCs. Ghrelin downregulatedLPS/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 activationwere abolished by D-Lys-3-GHRP-6. These results showed that ghrelin inhibits LPS/leptin-induced MUC5AC overex-pression 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 si-nonasal diseases.
Abstract
Objectives. Obesity, which induces chronic low-grade systemic inflammation in the human body, is a known risk factor forvarious diseases. Recent studies have shown associations between various otorhinolaryngological diseases and obesi-ty. In particular, inflammatory sinonasal diseases have been found to be strongly associated with obesity-related pro-inflammatory mediators. Many studies have been conducted to identify therapeutic agents for controlling obesity-re-lated inflammatory airway diseases. Ghrelin, an endogenous peptide from the stomach, has anti-inflammatory andantioxidative effects in a wide range of tissues. However, the effect of ghrelin on the regulation of mucus secretionhas not yet been studied in the human nasal mucosa. Therefore, we investigated the effects of ghrelin on lipopolysac-charide (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 ex-amined using reverse transcription polymerase chain reaction, real-time polymerase chain reaction, enzyme immu-noassays, Western blotting, and immunofluorescence staining. Results. Growth hormone secretagogue receptor 1a (GHSR1a) was expressed in the HNEpCs. Ghrelin downregulatedLPS/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 activationwere abolished by D-Lys-3-GHRP-6. These results showed that ghrelin inhibits LPS/leptin-induced MUC5AC overex-pression 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 si-nonasal diseases.
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