Regulation of surfactant secretion in alveolar type II cells

Андреева, А. В.; Kutuzov, Mikhail A.; Voyno-Yasenetskaya, Tatyana A.

doi:10.1152/ajplung.00112.2007

Cited by 189 publications

(165 citation statements)

References 179 publications

(202 reference statements)

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“…Lung surfactant forms a lipid monolayer at the interface of liquid and air and reduces the surface tension along the alveolar, leading to lowering the work of breathing and preventing alveolar collapse at expiration (35). In addition, it is well known that PGE 2 induces relaxation in the airways (8).…”

Section: Discussionmentioning

confidence: 99%

Proteinase-Activated Receptor-2–Triggered Prostaglandin E2 Release, but Not Cyclooxygenase-2 Upregulation, Requires Activation of the Phosphatidylinositol 3–Kinase / Akt / Nuclear Factor-κB Pathway in Human Alveolar Epithelial Cells

et al. 2009

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Abstract. Proteinase-activated receptor-2 (PAR2) triggers upregulation of cyclooxygenase-2 (COX-2) and prostaglandin E 2 (PGE 2 ) formation in human alveolar epithelial A549 cells. This COX-2 upregulation appears to involve the Src / epidermal growth factor (EGF) receptor / p38 MAP kinase (p38MAPK) pathway and also the cAMP-response element-binding protein (CREB) pathway. Here, we investigated the roles of nuclear factor-κB (NF-κB)-related signals in the PAR2-triggered PGE 2 release / COX-2 upregulation in A549 cells. The PAR2-triggered PGE 2 release was clearly blocked by an inhibitor of the NF-κB pathway. Stimulation of PAR2 actually caused phosphorylation of inhibitor-κB, an indicator of NF-κB activation, an effect being blocked by inhibitors of MEK, phosphatidylinositol 3-kinase (PI3-kinase), and Akt, but little or not by inhibitors of p38MAPK and JNK. Stimulation of PAR2 also caused phosphorylation of Akt, an effect suppressed by inhibitors of PI3-kinase and MEK. Nonetheless, the PAR2-triggered upregulation of COX-2 was resistant to inhibitors of NF-κB, PI3-kinase, and Akt, but was attenuated by inhibitors of MEK and JNK. Stimulation of PAR2 induced phosphorylation of CREB, an effect abolished by an inhibitor of MEK but not inhibitors of p38MAPK and EGF receptor. These findings demonstrate that the MEK / ERK / PI3-kinase / Akt / NF-κB pathway is involved in PAR2-triggered PGE 2 formation, but not upregulation of COX-2 that is dependent on activation of ERK /CREB and JNK in addition to p38MAPK.

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Section: Discussionmentioning

confidence: 99%

Proteinase-Activated Receptor-2–Triggered Prostaglandin E2 Release, but Not Cyclooxygenase-2 Upregulation, Requires Activation of the Phosphatidylinositol 3–Kinase / Akt / Nuclear Factor-κB Pathway in Human Alveolar Epithelial Cells

et al. 2009

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“…[6][7][8][9] Fundamental to these systems, fluid storage is itself an active, finely regulated balance. Storage droplets or vesicles continuously adjust their size, shape and contents through ongoing exchange with the surroundings, creating intrinsically responsive control mechanisms that tie secretion to a wide range of chemical and physical stimuli and feedback signals.…”

mentioning

confidence: 99%

Dynamic polymer systems with self-regulated secretion for the control of surface properties and material healing

et al. 2015

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Approaches for regulated fluid secretion, which typically rely on fluid encapsulation and release from a shelled compartment, do not usually allow for a fine, continuous modulation of secretion, and can be difficult to adapt for monitoring or functionintegration purposes. 1-5 Here, we report self-regulated, self-reporting secretion systems consisting of liquid-storage compartments in a supramolecular polymer-gel matrix with a thin liquid layer on top, and demonstrate that dynamic liquid exchange between the compartments, matrix and surface layer allows for repeated, responsive self-lubrication of the surface layer and for cooperative healing of the matrix. Depletion of the surface liquid or local material damage induces self-regulated secretion of the stored liquid via a dynamic feedback between polymer crosslinking, droplet shrinkage and liquid transport that can be read out through changes in the system's optical transparency. We envision diverse applications in fluid delivery, wetting and adhesion control, and material self-repair.Nearly every form of living tissue autonomously packages, transports, and secretes fluids, mediating defense, adhesion, wound healing, temperature -often several of these at once -through tightly self-regulated release systems. [6][7][8][9] Fundamental to these systems, fluid storage is itself an active, finely regulated balance. Storage droplets or vesicles continuously adjust their size, shape and contents through ongoing exchange with the surroundings, creating intrinsically responsive control mechanisms that tie secretion to a wide range of chemical and physical stimuli and feedback signals. [10][11][12][13] At the same time, collective changes in the stores are reported to the organism, alerting it that it needs to drink or eat to replenish the limited supply. Many synthetic approaches have been developed to enable triggered release from microcapsules, hydrogels, nanoparticles, vesicles, micelles, mesoporous carriers and other containers. [1][2][3][4][5][14][15][16][17] While these systems can secrete fluid in response to various stimuli, it remains a challenge to design a synthetic approach that displays finely tuned, continuous self-adjustment, integrated functionalities, and continuous liquid supply monitoring.2 Figure 1. Schematic of the self-regulated, liquid secretion system. Secretion liquid is stored as shell-less droplets inside a gel matrix composed of dynamic polymers, with ongoing liquid exchange between droplet and gel phases. If S = γ ga -(γ la + γ gl ) > 0, the matrix surface will be coated with a thin liquid overlayer. When this layer is removed, the disjoining pressure will trigger secretion of the stored liquid to restore the original film thickness, while the supramolecular gel matrix reconfigures through reversible bond disassembly and reassembly to release any buildup of mechanical stress due to shrinking droplets. With successive removal/restoring cycles, the liquid droplets will continuously shrink and the gel will become progressively transparent.Inspire...

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“…The lung surfactant consists of phospholipids, cholesterol and proteins, and is primarily produced by alveolar type II cells [5,6]. It forms a thin lipid layer on the surface of alveoli, which reduces surface tension and prevents alveoli from collapse during expiration.…”

mentioning

confidence: 99%

Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

Bækvad-Hansen¹,

Nordestgaard²,

Dahl³

2010

Eur Respir J

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The surfactant protein (SP)-B gene may influence chronic obstructive pulmonary disease (COPD) and, thus, personalised medicine. We tested whether functional polymorphisms in SP-B (rs1130866 (1580T.C), rs2077079 (-18A.C) and rs3024791 (-384G.A)) associate with reduced lung function and risk of COPD in the general population.We genotyped 10,231 individuals from the general adult Danish population, and recorded spirometry and hospital admissions due to COPD. Because we previously found an association between the rare SP-B 121ins2 mutation and COPD among smokers, we stratified the analyses for smoking status.None of the individual SP-B genotypes or genotype combinations were associated with reduced forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/ FVC overall or among smokers (p50.25-0.99). The odds ratio for spirometrically defined COPD did not differ from 1.0 for any of the SP-B genotypes or genotype combinations overall or among smokers (p50.17-0.78). Similar results were obtained for hospitalisation due to COPD (p50.07-0.93); we could exclude overall hazard ratios for heterozygotes of 1.18-1.21 and for homozygotes of 1.25-1.57 or larger for all three polymorphisms.In conclusion, the functional rs1130866, rs2077079 and rs3024791 polymorphisms in the SP-B gene are not associated with reduced lung function or risk of COPD, making it unlikely that these variants will be useful in personalised medicine.

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Regulation of surfactant secretion in alveolar type II cells

Cited by 189 publications

References 179 publications

Proteinase-Activated Receptor-2–Triggered Prostaglandin E2 Release, but Not Cyclooxygenase-2 Upregulation, Requires Activation of the Phosphatidylinositol 3–Kinase / Akt / Nuclear Factor-κB Pathway in Human Alveolar Epithelial Cells

Proteinase-Activated Receptor-2–Triggered Prostaglandin E2 Release, but Not Cyclooxygenase-2 Upregulation, Requires Activation of the Phosphatidylinositol 3–Kinase / Akt / Nuclear Factor-κB Pathway in Human Alveolar Epithelial Cells

Dynamic polymer systems with self-regulated secretion for the control of surface properties and material healing

Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

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