ABSTRACT
BACKGROUND/AIMS: Gastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia. Recent studies showed that hormones induced by stress are correlated with visceral hypersensitivity. However, the precise mechanisms underlying gastric hypersensitivity remain largely unknown. The aim of the present study was designed to investigate the roles of corticosterone (CORT) on excitability of dorsal root ganglion (DRG) neurons innervating the stomach. METHODS: DRG neurons innervating the stomach were labeled by DiI injection into the stomach wall. Patch clamp recordings were employed to examine neural excitability and voltage-gated sodium channel currents. Electromyograph technique was used to determine the responses of neck muscles to gastric distension. RESULTS: Incubation of acutely isolated DRG neurons with CORT significantly depolarized action potential threshold and enhanced the number of action potentials induced by current stimulation of the neuron. Under voltage-clamp mode, incubation of CORT enhanced voltage-gated sodium current density of the recorded neurons. Pre-incubation of GF109203X, an inhibitor of protein kinase C, blocked the CORT-induced hyperexcitability and potentiation of sodium currents. However, pre-incubation of H-89, an inhibitor of protein kinase A, did not alter the sodium current density. More importantly, intraperitoneal injection of CORT produced gastric hypersensitivity of healthy rats, which was blocked by pre-administration of GF109203X but not H-89. CONCLUSIONS: Our data strongly suggest that CORT rapidly enhanced neuronal excitability and sodium channel functions, which is most likely mediated by protein kinase C but not protein kinase A signaling pathway in DRG neurons innervating the stomach, thus underlying the gastric hypersensitivity induced by CORT injection.
Subject(s)
Animals , Humans , Rats , Abdominal Pain , Action Potentials , Corticosterone , Cyclic AMP-Dependent Protein Kinases , Diagnosis-Related Groups , Dyspepsia , Ganglia , Ganglia, Spinal , Hypersensitivity , Injections, Intraperitoneal , Neck Muscles , Neurons , Protein Kinase C , Protein Kinases , Sodium , Sodium Channels , Spinal Nerve Roots , Stomach , Visceral PainABSTRACT
PURPOSE: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Exosomes or extracellular vesicles are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in allergic diseases. In this study, we characterized the microRNA (miRNA) content of exosomes in AR. METHODS: Extracellular vesicles were isolated from nasal mucus from healthy control subjects (n=10) and patients with severe AR (n=10). Vesicle RNA was analyzed by using a TaqMan microRNA assays Human Panel-Early Access kit (Applied Biosystems, Foster City, CA, USA) containing probes for 366 human miRNAs, and selected findings were validated with quantitative RT-PCR. Target prediction and pathway analysis for the differentially expressed miRNAs were performed using DIANA-mirPath. RESULTS: Twenty-one vesicle miRNAs were up-regulated and 14 miRNAs were under-regulated significantly (P<0.05) in nasal mucus from AR patients when compared to healthy controls. Bioinformatic analysis by DIANA-mirPath demonstrated that 32 KEGG biological processes were significantly enriched (P<0.05, FDR corrected) among differentially expressed vesicle miRNA signatures. Among them, the B-cell receptor signaling pathway (P=3.709E-09), the natural killer cell-mediated cytotoxicity (P=8.466E-05), the T-cell receptor signaling pathway (P=0.00075), the RIG-I-like receptor signaling pathway (P=0.00127), the Wnt signaling pathway (P=0.00130), endocytosis (P=0.00440), and salivary secretion (P=0.04660) were the most prominent pathways enriched in quantiles with differential vesicle miRNA patterns. Furthermore, miR-30-5p, miR-199b-3p, miR-874, miR-28-3p, miR-203, and miR-875-5p, involved in B-cell receptor and salivary secretion signaling pathways, were selected for validation using independent samples from 44 AR patients and 20 healthy controls. MiR-30-5p and miR-199b-3p were significantly increased in extracellular vesicles from nasal mucus when compared to healthy controls, while miR-874 and miR-28-3p were significantly down-regulated. In addition, miRNA-203 was significantly increased in AR patients, while miRNA-875-5p was found to be significantly decreased in AR patients. CONCLUSIONS: This study demonstrated that vesicle miRNA may be a regulator for the development of AR.
Subject(s)
Humans , B-Lymphocytes , Biological Phenomena , Endocytosis , Epithelial Cells , Exosomes , MicroRNAs , Mucus , Receptors, Antigen, T-Cell , Rhinitis , RNA , Wnt Signaling PathwayABSTRACT
OBJECTIVE@#To explore the expression of Eotaxin and the effect of histamine in allergic rhinitis model (AR), and aim to explore the pathogenesis of AR.@*METHOD@#The AR models were established by application of ovum albumin in rats. The expression of Eotaxin in nasal mucosa, serum and nasal cavity lavage fluid, were observed before and after treatment of histamine or its antagonist by immunochemistry, RT-PCR and ELISA technique.@*RESULT@#The expression of Eotaxin in nasal lavage fluid and nasal mucosa increased after treatment of histamine (P < 0.05). Contrarily, the expression of Eotaxin in nasal lavage fluid, nasal mucosa and serum decreased after treatment of the antagonist of histamine.@*CONCLUSION@#Both histamine and its receptor can involve in the pathogenesis of AR by affecting the expression of Eotaxin.
Subject(s)
Animals , Female , Male , Rats , Chemokine CCL11 , Metabolism , Histamine , Metabolism , Nasal Mucosa , Metabolism , Rats, Sprague-Dawley , Rhinitis, Allergic, Perennial , Metabolism , Pathology , Rhinitis, Allergic, Seasonal , Metabolism , PathologyABSTRACT
Objective: To explore the expression of Eotaxin and the effect of histamine in allergic rhinitis model (AR),and aim to explore the pathogenesis of AR. Method:The AR models were established by applicating of ovain albumin in rats. The expression of Eotaxin in nosal mucosa,serum and nasal cavity lavage fluid,were observed before and after treatment of histamine or its antagonist by immunochemistry,RT-PCR and ELISA technique. Result:The expression of Eotaxin in nasal lavage fluid and nasal mueosa increased after treatment of histamine(P＜0.05). Contrarily,the expression of Eotaxin in nasal lavage fluid,nasal mucosa and serum decreased after treatment of the antagonist of histamine. Conclusion:Both histamine and its receptor can involve in the pathogenesis of AR by affecting the expression of Eotaxin.
ABSTRACT
OBJECTIVE@#To study the change of endogenous hydrogen sulfide (hydrogen sulfide, H2S) and its rate-limiting enzyme Cystathionine-gamma-lyase (CSE) in allergic rhinitis through guinea pigs with intervention treatment.@*METHOD@#Twenty-four guinea pigs were divide into 4 groups at random, one group were models of allergic rhinitis (AR) which were established by using ovalbumin, the second group were treated with NaHS after sensitized, the third group were treated with Propargylglycine (PPG) which was suppression of CSE after sensitized, and the last group were treated with saline for control. The concentration of eotaxin of nasal lavage and H2S in plasma were recorded, and then the expression of CSE in nasal mucosa was determined by real-time fluorescence RT-PCR.@*RESULT@#The concentration of eotaxin in nasal lavage of sensitized group were higher than those of control (P < 0.01), and concentration of H2S in plasma and expression of CSE in nasal mucosa were lower than control (P < 0.05). The concentration of eotaxin decreased when treated with NaHS and increased when treated with PGG (P < 0.05). Level of H2S in plasma and expression of CSE increased when treated with NaHS and decreased when treated with PGG (P < 0.05), and the level of H2S was positive linear correlate with the expression of CSE.@*CONCLUSION@#Endogenous H2S perhaps plays a significant role in the pathogenesis of allergic rhinitis, and it was mainly regulated by CSE.