The construction and application of online open courses in Chinese colleges and universities--Taking the physiology course at Central South University of China as an example / 生理学报

Massive open online course (MOOC) is a new learning model, which integrates the progress of novel educational concepts and the breakthrough of information technology. MOOC uses new web-based tools and online-environments to deliver knowledge education and lecture classes in a new paradigm. In this paper, we firstly reviewed the achievements through four stages of the construction and development of online courses of physiology in China in the past 20 years. Then, taking the physiology MOOC at Central South University of China as an example, we introduced the specific practices and experiences to construct the online physiological open course, including the online open course-based offline and online flipped classroom teaching practice. Finally, we discussed several important issues during the construction and application of online open courses, aiming to provide practical information for other universities.

Research progress of endogenous bone marrow-derived mesenchymal stem cells in pulmonary fibrosis / 生理学报

Pulmonary fibrosis is a chronic, diffuse, interstitial lung disease involving the pulmonary interstitium, alveoli, and bronchioles caused by various causes. There is no effective treatment. Currently, exogenous bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation has attracted much attention as a new stem cell therapy in the treatment of pulmonary fibrosis. Less attention has been paid to the functional status of endogenous BM-MSCs during pulmonary fibrosis. Based on summary on the anti-pulmonary fibrosis effect of BM-MSCs and its mechanism, this review further discusses the abnormal changes of bone marrow function in animals with pulmonary fibrosis and the role of glutamate NMDA receptor overactivation in mediating the functional inhibition of endogenous BM-MSCs induced by pulmonary fibrosis. This will provide potential ideas for finding effective treatments for pulmonary fibrosis.

The metabolic networks of ferroptosis and links to lung diseases / 生理学报

Ferroptosis is a newly discovered non-apoptotic form of regulated cell death driven by iron-dependent lipid peroxidation. The present studies have shown that many metabolic processes and homeostasis are affected by ferroptosis. It is related to many lung diseases, including acute lung injury, chronic obstructive pulmonary disease and pulmonary fibrosis, etc. Currently, the research on ferroptosis is still in its infancy. Previous studies have confirmed that ferroptosis is regulated by a variety of genes, and the mechanism is complex, mainly involving iron homeostasis and lipid peroxidation metabolism. This review summarizes some regulation networks of metabolic processes associated with ferroptosis and discusses the roles of ferroptosis in the pathophysiological progression of many lung diseases. We expected to provide new ideas and references for the treatment of these diseases.

ERα36 is involved in the proliferation promotion and anti-apoptosis effects of icaritin on MG63 cells / 生理学报

The mechanism for icaritin to improve postmenopausal osteoporosis (PMOP) has not been clarified. The aim of this study was to investigate the role of estrogen receptor α36 (ERα36) in the proliferation promotion and anti-apoptosis effects of icaritin on osteoblasts and the underlying mechanism of downstream signal transduction. The ERα36 knockdown human osteosarcoma MG63 cell model was constructed by transfection of shRNA vector. Cell proliferation was detected by CCK-8, the apoptosis was detected by flow cytometry, and the activation of ERK and AKT signaling pathways was detected by Western blot. The results showed that the effects of icaritin on the proliferation and apoptosis of MG63 cells were significantly decreased after ERα36 knockdown, and icaritin could up-regulate the levels of ERK and AKT phosphorylation in MG63 cells, which could be reduced by ERα36 knockdown. The effect of icaritin on the proliferation of MG63 cells was significantly decreased by pretreating the cells with U0126 (an ERK signaling pathway blocker) and LY294002 (an AKT signaling pathway blocker), respectively. Furthermore, anti-apoptotic effect of icaritin on MG63 cells was significantly decreased after the cells were pretreated with U0126, but not with LY294002. These results suggest that icaritin exerts proliferation promotion and anti-apoptosis effects on osteoblasts through ERα36 and its downstream ERK and AKT signaling pathways.

LIMR is involved in the inhibitory effect of antiflammin-1 on epithelial-mesenchymal transition in A549 cells / 生理学报

Epithelial-mesenchymal transition (EMT) occurring in alveolar epithelial cells plays an important role in the development and progression of pulmonary fibrosis. Previous studies showed that antiflammin-1 (the active fragment of uteroglobin) effectively inhibited bleomycin-induced pulmonary fibrosis. However, its mechanism is still far from being clarified. In this study, we investigated the effects of antiflammin-1 on EMT in A549 cells induced by transforming growth factor-β1 (TGF-β1) and the underlying mechanism by using morphological observation and Western blot. The results showed that the expression of α-smooth muscle actin (α-SMA) increased significantly while the expression of E-cadherin decreased significantly in A549 cells following treatment with TGF-β1 concomitant with morphological change of A549 cells from pebble-like shape epithelial cells to spindle-like mesenchymal shape. This process of EMT in A549 cells induced by TGF-β1 was significantly inhibited when A549 cells were co-incubated with TGF-β1 and antiflammin-1. Furthermore, the anti-lipocalin interacting membrane receptor (LIMR) antibody and PD98059 (an ERK signaling pathway blocker) attenuated the inhibitory effect of antiflammin-1 on TGF-β1-induced EMT, respectively. Our findings indicate that antiflammin-1 can inhibit EMT in A549 cells induced by TGF-β1, which is related to LIMR and its downstream ERK signaling pathway.

The platelet-producing function of lung / 生理学报

It is generally believed that platelets are cytoplasmic bodies with biological activity falling off the cytoplasm of megakaryocytes from bone marrow. However, a large number of megakaryocytes have been found in the lung tissue in many researches. Whether the lung has the function of producing platelets has been controversial. In this paper, we briefly review the proposition, early stage researches, the latest confirmations and possible meaning of the hypothesis of platelet-producing function of lung.

Metabotropic glutamate receptor 8 activation promotes the apoptosis of lung carcinoma A549 cells in vitro / 生理学报

This study aims to detect the expression of metabotropic glutamate receptors (mGluRs) in lung carcinoma A549 cells, and to investigate the effects of mGluR8 and mGluR4 activation on the growth of A549 cells in vitro. The mRNA expression levels of the 8 subtypes of mGluRs in A549 cells were determined by real-time PCR. Immunohistochemistry was used to analyze the protein expression of mGluR4 and mGluR8 in A549 cells and lung tissue sections obtained from lung adenocarcinoma patients. To observe the effects of mGluR8 and mGluR4 activation on the growth of A549 cells, the cultured cells were treated with (S)-3,4-DCPG (an agonist of mGluR8) and VU0155041 (an agonist of mGluR4), respectively, and then the cell viability was analyzed by CCK-8 kit, the percentage of DNA synthesis was detected by EdU incorporation, and the apoptosis of the cells was measured by hoechst 33258 staining and flow cytometry. The results showed that there were low expressions of mGluR1, mGluR5, mGluR6, mGluR7 mRNA, no expression of mGluR2 and mGluR3 mRNA, and high expressions of mGluR8 and mGluR4 mRNA in A549 cells. Accordingly, there were also mGluR4 and mGluR8 protein expressions in the A549 cells and the lung adenocarcinoma tissue sections. VU0155041 had no effect on the growth of A549 cells, but (S)-3,4-DCPG significantly decreased the cells' growth in a dose-dependent manner and increased the apoptosis of the cells. The results revealed a role of mGluR8 in the growth and apoptosis of A549 cells and suggested a potential target for clinical treatment of lung cancer.

Changes in fasting serum cortisol levels in adolescents with type 1 diabetes and elevated depressive symptoms / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the changes in serum cortisol levels in adolescents with type 1 diabetes (T1DM) and elevated depressive symptoms.</p><p><b>METHODS</b>Twenty-eight adolescents with T1DM and 31 healthy peers were assessed for depressive symptoms using a depression self-rating scale developed by the Epidemiological Survey Center. Selected subjects were classified into four groups: T1DM with elevated depressive symptoms group (n=15), T1DM without elevated depressive symptoms group (n=13), elevated depressive symptoms without T1DM group (n=15), and normal control group (n=16). Fasting blood samples were collected in the morning, and the levels of serum cortisol were compared among the four groups. The correlations of serum levels of cortisol and glycosylated hemoglobin A1c (HbA1c) with the score of depression self-rating scale were evaluated by Pearson correlation analysis.</p><p><b>RESULTS</b>The fasting serum cortisol levels in the 28 T1DM patients were significantly higher than in the 31 healthy peers (P<0.01). The fasting cortisol levels in the T1DM with elevated depressive symptoms group were significantly higher compared with those in the elevated depressive symptoms without T1DM group and normal control group (P<0.01). In adolescents with T1DM, serum HbA1c level was positively correlated with the score of depression self-rating scale (r=0.481, P=0.010).</p><p><b>CONCLUSIONS</b>The fasting serum cortisol levels in adolescents with T1DM and elevated depressive symptoms are significantly increased, suggesting that the patients with comorbidity of T1DM and depression develop dysfunction of the corticotropin-releasing hormone-adrenocorticotropic hormone-cortisol axis. The elevated depressive symptoms may be associated with a poor control of glucose metabolism.</p>

Bioinformatics of mouse uteroglobin binding protein and its polyclonal antibody preparation / 生理学报

To prepare anti-mouse uteroglobin binding protein (mUGBP) polyclonal antibody, two polypeptides were synthesized based on the bioinformatics analysis of mUGBP, and New Zealand white rabbits were immunized separately with each peptide coupled with keyhole limpet hemocyanin (KLH). The data indicate that a 13-amino acid polypeptide (positions 221st-233rd) was able to generate anti-peptide antibodies. The titer of the antisera detected with ELISA was 1:10(8). The antisera were then purified with immuno-affinity chromatography to obtain antibodies. Western blot analysis of mUGBP expressed as a fusion protein with a green fluorescent protein (GFP) was performed on the cell lysates of COS-1 cells with the purified antisera, suggesting that the antisera specifically recognized UGBP. By immunohistochemistry and indirect immunofluorescence analysis, we examined the expression of UGBP in the lung tissues from a patient undergoing surgical lung resection for a tumor and from normal mouse lung tissue, and found for the first time that UGBP protein was widely expressed in both mouse and human lung tissue with the most abundant expression in bronchial epithelial cells. These results suggest that the antigen epitopes of mUGBP are well predicted by using bioinformatics analysis. We have obtained anti-mUGBP polyclonal antibody, which will be useful for further investigation.

Role of uteroglobin-binding protein in antiflammin-1 promoting IL-10 expression and secretion in RAW264.7 cells induced by endotoxin / 生理学报

The present study investigated the effect of antiflammin-1 (AF-1) on LPS-induced IL-10 secretion from RAW264.7 cells through uteroglobin-binding protein (UGBP). Cultured RAW264.7 cells, a murine monocyte-macrophage cell line, were divided as following: control group, LPS group (1 µg/mL LPS), AF-1 group (100 μmol/L AF-1), LPS+AF-1 group (2 h of 100 μmol/L AF-1 pretreatment before LPS addition), and LPS+AF-1+anti-UGBP group (30 min of anti-UGBP antibody pretreatment before successive treatments with AF-1 and LPS). IL-10 concentration in the supernatants was detected by ELISA assay, and the level of IL-10 mRNA expression in macrophage was detected by using RT-PCR method. The results showed that AF-1 significantly increased LPS-induced IL-10 secretion in RAW264.7 cells in a dose dependent way, and up-regulated its mRNA level. Anti-UGBP antibody pretreatment attenuated the augmented effect of AF-1 on LPS-induced IL-10 secretion and gene expression. These results suggest that AF-1 promotes LPS-induced IL-10 secretion from macrophages, and this effect is mediated by UGBP.

Activation of mGluRI in neutrophils promotes the adherence of neutrophils to endothelial cells / 生理学报

L-glutamate (Glu) is an excitatory neurotransmitter in the mammalian central nervous system. Relatively much attention has been paid to functional expression of Glu signaling molecules in peripheral tissues very recently. The present study tested the hypothesis that the activation of group I metabotropic glutamate receptor (mGluRI) in neutrophils stimulated neutrophils adherence to endothelial cells by increasing the surface expression of certain adhesion molecules. Peripheral blood was obtained by venipuncture from healthy donors, and the neutrophils were isolated by Ficoll-Hypaque gradient centrifugation. Neutrophils floating into DMEM/F12 culture medium containing 10% fetal bovine serum were then used immediately. Immunocytochemistry and real-time quantitative RT-PCR were used to detect the expression of mGluRI (mGluR1 and mGluR5) in neutrophils. The adherence of neutrophils to cultured human normal umbilical vein endothelial cells (HUVE-12) was measured by the colorimetric method. Cell surface expression of adhesion molecule CD11a in the neutrophils was determined by flow cytometry. Immunocytochemistry and real-time quantitative RT-PCR showed that mGluR1 and mGluR5 were constitutively expressed in neutrophils. Application of mGluRI agonist S-3,5-dihydroxyphenylglycine (S-DHPG) (1x10(-8)-1x10(-6) mol/L) showed a dose-dependent stimulatory effect on the adherence of neutrophils to HUVE-12 (P<0.05 or P<0.01), with a maximum effect at 1x10(-6) mol/L (P<0.01). Incubations as short as 30 min were sufficient to induce increased adherence after the beginning of S-DHPG treatment. Following time extension (0.5-5 h), S-DHPG (1x10(-6) mol/L) increased the rate of neutrophils adhesion to HUVE-12 with a maximum effect at 0.5 h (P<0.01). However, a time-dependent effect of S-DHPG on the rate of neutrophils adhesion to HUVE-12 was not observed during the experimental period. 1x10(-6) mol/L of S-DHPG also induced an increased surface expression of adhesion molecule CD11a (P<0.01) when neutrophils were preincubated with 1x10(-6) mol/L of S-DHPG for 1 h. Furthermore, the specific mGluRI antagonist (RS)-alpha-methyl-4-carboxyphenylglycine ((+/-)-MCPG, 0.5 mmol/L) significantly abolished the stimulatory effect of S-DHPG (1x10(-6) mol/L) on the adherence of neutrophils to HUVE-12 (P<0.01). These results suggest that the activation of mGluRI in neutrophils results in increased adhesion molecule CD11a expression and thereby promotes the adherence of neutrophils to endothelial cells.

High-density lipoprotein attenuates lipopolysaccharide-induced acute lung injury in mice / 生理学报

High-density lipoprotein (HDL), an abundant plasma lipoprotein, has been thought to be anti-inflammatory in both health and infectious diseases. It binds lipopolysaccharide (LPS) and neutralizes its bioactivity. The present study aimed to investigate the potential role of HDL, which was separated from human plasma, in LPS-induced acute lung injury in mice. Kunming mice (18-22 g) were treated with either HDL (70 mg/kg body weight, via tail vein) or saline 30 min after LPS administration (10 mg/kg body weight, intraperitoneally) and were decapitated 6 h after LPS challenge. The arterial blood was collected and analyzed for blood gas variables (PaO(2), pH, and PaCO(2)). The bronchoalveolar lavage fluid (BALF) samples were analyzed for total protein concentration, lactate dehydrogenase (LDH) activity, and white blood cell (WBC) count. The lung samples were taken for histopathological evaluation and for determination of lung wet-to-dry weight ratio (W/D), malondialdehyde (MDA) content, myeloperoxidase (MPO) activity and tumor necrosis factor α (TNF-α) content. Arterial blood gas analysis showed that after LPS challenge, HDL-treated mice exhibited a higher PaO(2), and pH, but a lower PaCO(2) than HDL-untreated ones (P<0.01). LPS-induced increases in total protein concentration, WBC number and LDH activity in BALF were significantly attenuated in HDL-treated mice (P<0.01). HDL treatment also resulted in a significant protection of lung tissues against LPS-induced acute lung injury via decreasing W/D ratio, MPO activity, MDA content, and the content of the pro-inflammatory cytokine TNF-α (P<0.05, P<0.01). Histological examination revealed that HDL treatment resulted in significantly lower scores of acute lung injury induced by LPS, with reduced hemorrhage, intra-alveolar edema and neutrophilic infiltration (P<0.01). It is suggested that HDL plays a protective role in attenuating LPS-induced acute lung injury in mice.

Experimental study of acute lung injury induced by glutamate in vivo / 中南大学学报(医学版)

OBJECTIVE@#To investigate the possible injury induced by glutamate in the lung.@*METHODS@#The lung wet weight/body weight (LW/BW), lung wet/dry weight (W/D), the content of cells and the total protein (TP) in bronchoalveolar lavage fluid (BALF) were determined together with the micromorphology observation.@*RESULTS@#(1) The LW/BW, W/D, the content of white blood cells, red blood cells and TP in BALF increased in a dose dependent manner 2 hours after the administration of the glutamate (0.50 - 0.75 g/kg). (2) Examination of histological sections showed the presence of lung inflammation charactered by neutrophils recruitment 2 hours after the glutamate administration. (3) The increase of W/D caused by glutamate (0.50 g/kg) was nearly abolished by pre-treatment with MK801 (a specific blocker of NMDA receptor, 0.1 mg/kg) for 30 minutes (P<0.05).@*CONCLUSION@#Glutamate can cause the acute lung injury through the activation of NMDA receptor in vivo.

The neuroprotective effects and its mechanisms of qingkailing injection on bacterial meningitis induced by E. coli in rabbits / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the neuro-protective effect and mechanism of qingkailing injection (QKL) against cerebral injury caused by E. coli-meningitis (CM).</p><p><b>METHODS</b>The CM model rabbits were treated by ampicillin with QKL as adjuvant. The leukocyte count and protein content in cerebral spinal fluid (CSF), the contents of water, sodium, potassium and calcium in cerebral tissues were measured before, 16 h and 26 h after Bacillus coli injection respectively. The expression of matrix metalloproteinase-9 (MMP-9) was determined at the same time.</p><p><b>RESULTS</b>Adjunctive treatment with QKL can not only inhibit the increase of leukocyte cells, protein content in CSF, and water, sodium, calcium content in cerebral tissues, but also the decrease of potassium content revealed during simple antibiotic treatment. It also can decrease the expression of MMP-9 in cerebral tissues of rabbits with CM.</p><p><b>CONCLUSION</b>As an adjunctive treatment, QKL can prevent transient inflammatory reaction and aggravation of brain injury in CM induced by simple antibiotic treatment, its mechanisms might relate with calcium antagonism and attenuation of MMP-9 expression in brain tissues.</p>

Influence of vasoactive intestinal peptide on expression of pulmonary surfactant associated protein A in lung explants / 中国应用生理学杂志

<p><b>AIM</b>To study the influence of VIP on the expression of SP-A and its intracellular signal transduction pathway.</p><p><b>METHODS</b>The influence of VIP on the expression of SP-A was studied by immunohistochemistry and RT-PCR. The intracellular signal transduction pathway was further investigated by using receptor antagonist, protein kinase inhibitor and antisense oligonucleotides.</p><p><b>RESULTS</b>(1) VIP(10(-8) mol/L) enhanced SP-A protein expression in alveolar type II cells (ATII) and increased the content of SP-A mRNA in lung tissue. (2) VIP receptor antagonist [D-P-C1-Phe (6)-Leu (17)]-VIP (10(-6) mol/L) could suppress the VIP-induced expression of SP-A protein and SP-A mRNA. (3) c-fos antisense oligonucleotides (9 x 10(-6) mol/L) could inhibit the VIP-induced expression of SP-A protein and SP-A mRNA. (4) Protein kinase C(PKC) inhibitor H7 (10(-5) mol/L) could also depress the V1P-induced SP-A protein and SP-A mRNA.</p><p><b>CONCLUSION</b>VIP can up-regulate the expression of SP-A through its receptor. PKC and c-fos protein play important roles in the intracellular signal transduction pathway through which VIP induces the expression of SP-A.</p>

Temporal and spatial distribution of VIP, CGRP and their receptors in the development of airway hyperresponsiveness in the lungs / 生理学报

To explore the role of intrapulmonary neuropeptides in the development of airway hyperresponsiveness, we established an animal model of airway hyperresponsiveness (AHR) in rabbits by using ozone exposure. With the model, after test of the mechanics of respiration and bronchoalveolar lavage assay, the levels of vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) in the lungs were determined by radioimmunoassay, and the expression of mRNA coding receptors of these two neuropeptides was evaluated by reverse transcriptional-polymerase chain reaction (RT-PCR). At the same time, the distribution of VIP receptor-1 (VIPR1) and CGRP receptor-1 (CGRPR1) in lung tissues and its time-course were examined by in situ hybridization. The results showed: (1) in ozone-stressing groups, airway resistance increased significantly and typical inflammatory pathological changes were observed in pulmonary tissue slides, including neutrophil and eosinophil infiltration, mucus exudation and bronchial epithelial cells (BECs) shedding; (2) with elongation of ozone exposure, the levels of VIP and CGRP in the lungs increased at first, reaching a peak on d 2 to 4, then decreased slowly, and CGRP peaked somewhat earlier than VIP; (3) mRNA expression of the two neuropeptide receptors in the lungs changed in a similar manner like VIP and CGRP, but the high level of mRNA expression of VIPR1 lasted longer than that of CGRPR1; and (4) in situ hybridization for neuropeptide receptors demonstrated that, in unstressed control, VIPR1 and CGRPR1 positive cells appeared in the airway epithelium, pulmonary interstitial and focal areas of airway and vascular smooth muscles. With the elongation of ozone exposure, hybridization stained deeper and the majority of positive cells were located around the vessels and bronchus except a few in the alveoli. At 8 d, only a small number of positive cells were seen in the lungs. From the results, it is concluded that ozone-stressing can induce the development of AHR, in which VIP and CGRP may play important roles. That implies, through binding to CGRPR1, CGRP stimulates an early inflammation response which contributes in cleaning up of irritants, while VIP exerts a later dampening of pulmonary inflammation response. These two neuropeptides may play sequential and complementary roles in the development of AHR.

Fibronectin upregulates catalase gene expression in rabbit bronchial epithelial cells / 生理学报

We have previously shown that the binding of integrins with extracellular matrix component fibronectin (Fn) can improve the ability of bronchial epithelial cells (BECs) in resisting oxidant injury by up-regulating the activity of catalase and increasing the content of GSH. However, the molecular mechanism or its signaling pathway of this protection is still unclear. In order to examine the intracellular signaling mechanism activated by Fn-integrin binding reaction, the present study investigated the mRNA expression of catalase in primary cultured rabbit BECs using RT-PCR based on a cell-injury model made with ozone exposure. The product bands of target gene CAT were checked with Southern blot and oligonucleotide probe hybridization. The results showed that Fn (10 microg/ml) promoted the catalase mRNA transcription (P<0.01). This effect was abolished either by protein-tyrosine kinase inhibitor genistein or calmodulin inhibitor W(7) (P<0.01). These results indicate that the promotion of catalase activity induced by Fn-integrin reaction is partly due to the elevation of catalase mRNA transcription, and that its signalling are possibly relevant to tyrosine phosphorylation or calmodulin pathway.

Effect of 17beta-estradiol on phosphorylcholine cytidylyltransferase activity from cultured rat lung explants / 中国应用生理学杂志

<p><b>AIM</b>To investigate the influence and mechanisms of 17beta-estradiol on the CTP: phosphorylcholine cytidylyltransferase (CCT) activity from cultured lung explants without serum.</p><p><b>METHODS</b>We detected the amount of [M-14C] choline incorporation into phosphatidylcholine so as to reflect CCT activity by liquid scintillation.</p><p><b>RESULTS</b>(1) 17beta-estradiol increased the CCT activity in dose-dependence and time-dependence. (2) Both the protein kinase C inhibitor H-7 and calmodulin antagonist W-7 abolished the stimulatory effect of 17beta-estradiol (3 x 10(-6) mol/L) on the CCT activity.</p><p><b>CONCLUSION</b>17beta-estradiol can increase CCT activity in cultured lung explants, its mechanism is related to protein kinase C and calmodulin.</p>

Regulatory peptides modulate ICAM-1 gene expression and NF-kappaB activity in bronchial epithelial cells / 生理学报

Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule leading to adhesion between cells; NF-kappaB, being universally distributed in the organism, is an important nuclear transcription factor leading to a rapid response to the stimuli. Line of evidence have shown that ICAM-1 transcription and NF-kappaB activation is an important step of inflammatory reaction. To testify that intrapulmonary regulatory peptides modulate inflammatory lesion of bronchial epithelial cells (BECs) through their effect on ICAM-1 expression and nuclear factor kappaB (NF-kappaB) activation, we used immunocytochemistry, RT-PCR, and electrophoretic mobility-shift assay (EMSA) to determine the ICAM-1 expression and NF-kappaB activity in BECs. The effects of NF-kappaB inhibitor MG-132 on ICAM-1 expression were also observed. The results showed that vasoactive intestinal peptide (VIP) and epidermal growth factor (EGF) decreased ICAM-1 expression in O(3)-stressed BECs, while endothelin-1 (ET-1) and calcitonin gene-related peptides (CGRP) increased ICAM-1 expression in resting BECs. MG-132 blocked ICAM-1 expression induced by O(3), ET-1 and CGRP. The results obtained by using EMSA confirmed that VIP and EGF restrained the activation of NF-kappaB in O(3)-stressed BECs; CGRP and ET-1 promoted activation of NF-kappaB. These observations indicate that VIP and EGF abated the injury by means of down-regulatory effects on ICAM-1 transcription and NF-kappaB activation, while ET-1 and CGRP enhanced the inflammation reaction by an up-regulatory effect. It is suggested that a developing and intensive airway inflammation correlates closely with a persistent expression of ICAM-1 and repeated activation of NF-kappaB.

Protective effect of low concentration endothelin-1 on the reactive oxygen-induced inhibition of pulmonary surfactant lipid synthesis / 生理学报

The effects of endothelin-1 (ET-1) at low concentration (1-100 pmol/L) on the reactive oxygen-induced inhibition of both pulmonary surfactant (PS) lipid synthesis and the activity of CTP: phosphorylcholine cytidylyltransferase (CCT), a rate-limiting enzyme in biosynthesis of phosphoatidylcholine (PC), were studied in cultured lung explants without serum. The xanthine-xanthine oxidase superoxide anion generating system decreased (3)H-choline incorporation into PC in a dose-dependent manner in cultured lung explants. ET-1 reduced both the reactive oxygen-induced decrease in (3)H-choline incorporation and the increase in malondialdehyde (MDA) content of lung tissues, but did not change the levels of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and the total antioxidant capability in the lung explants. ET-1 enhanced microsomal CCT activity of the lung tissues, while it decreased cytosolic CCT activity of lung tissues. ET-1 also prevented the inhibitive effect of reactive oxygen on microsomal CCT activity in the lung explants. These results suggest that ET-1 at low concentration can protect the microsomal CCT activity and reduce the inhibition of PS lipid synthesis induced by oxidant lung injury. The protective mechanism of ET-1 is not relative to the pulmonary endogenous antioxidant defense system.