scholarly journals TNF-α-Induced Cyclooxygenase-2 Expression in Human Lung Epithelial Cells: Involvement of the Phospholipase C-γ2, Protein Kinase C-α, Tyrosine Kinase, NF-κB-Inducing Kinase, and I-κB Kinase 1/2 Pathway

2000 ◽  
Vol 165 (5) ◽  
pp. 2719-2728 ◽  
Author(s):  
Ching-Chow Chen ◽  
Yi-Tao Sun ◽  
Jun-Jie Chen ◽  
Kuo-Tung Chiu
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Tyrosine Kinase ◽  
Human Lung ◽  
Lung Epithelial Cells ◽  
Kinase C ◽  
Tnf Α ◽  
Lung Epithelial ◽  
Human Lung Epithelial Cells

scholarly journals Role of protein kinase C in cytokine secretion by lung epithelial cells during infection withParacoccidioides brasiliensis

2015 ◽  
Vol 73 (7) ◽  
pp. ftv045 ◽  
Author(s):  
Cristiane Alcantara ◽  
Paloma Korehisa Maza ◽  
Bianca Carla Silva Campitelli Barros ◽  
Erika Suzuki
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Cytokine Secretion ◽  
Kinase C ◽  
Lung Epithelial

scholarly journals TNF Family Cytokines Induce Distinct Cell Death Modalities in the A549 Human Lung Epithelial Cell Line when Administered in Combination with Ricin Toxin

Toxins ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 450 ◽  
Author(s):  
Hodges ◽  
Kempen ◽  
McCaig ◽  
Parker ◽  
Mantis ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Human Lung ◽  
Lung Epithelial Cells ◽  
Lung Epithelial Cell ◽  
Distinct Cell ◽  
Tnf Α ◽  
Lung Epithelial ◽  
Human Lung Epithelial Cells

Ricin is a member of the ribosome-inactivating protein (RIP) family of toxins and is classified as a biothreat agent by the Centers for Disease Control and Prevention (CDC). Inhalation, the most potent route of toxicity, triggers an acute respiratory distress-like syndrome that coincides with near complete destruction of the lung epithelium. We previously demonstrated that the TNF-related apoptosis-inducing ligand (TRAIL; CD253) sensitizes human lung epithelial cells to ricin-induced death. Here, we report that ricin/TRAIL-mediated cell death occurs via apoptosis and involves caspases -3, -7, -8, and -9, but not caspase-6. In addition, we show that two other TNF family members, TNF-α and Fas ligand (FasL), also sensitize human lung epithelial cells to ricin-induced death. While ricin/TNF-α- and ricin/FasL-mediated killing of A549 cells was inhibited by the pan-caspase inhibitor, zVAD-fmk, evidence suggests that these pathways were not caspase-dependent apoptosis. We also ruled out necroptosis and pyroptosis. Rather, the combination of ricin plus TNF-α or FasL induced cathepsin-dependent cell death, as evidenced by the use of several pharmacologic inhibitors. We postulate that the effects of zVAD-fmk were due to the molecule’s known off-target effects on cathepsin activity. This work demonstrates that ricin-induced lung epithelial cell killing occurs by distinct cell death pathways dependent on the presence of different sensitizing cytokines, TRAIL, TNF-α, or FasL.

TNF-α induces cytosolic phospholipase A2 expression via Jak2/PDGFR-dependent Elk-1/p300 activation in human lung epithelial cells

2014 ◽  
Vol 306 (6) ◽  
pp. L543-L551 ◽  
Author(s):  
Chuen-Mao Yang ◽  
I-Ta Lee ◽  
Pei-Ling Chi ◽  
Shin-Ei Cheng ◽  
Li-Der Hsiao ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Lung ◽  
Growth Factor Receptor ◽  
Lung Epithelial Cells ◽  
Mapk Phosphorylation ◽  
Cytosolic Phospholipase ◽  
Tnf Α ◽  
Lung Epithelial ◽  
Phosphoinositide 3 Kinase ◽  
Human Lung Epithelial Cells

Cytosolic phospholipase A2 (cPLA2) plays a pivotal role in mediating agonist-induced arachidonic acid release for prostaglandin (PG) synthesis during inflammation triggered by tumor necrosis factor-α (TNF-α). However, the mechanisms underlying TNF-α-induced cPLA2 expression in human lung epithelial cells (HPAEpiCs) were not completely understood. Here, we demonstrated that TNF-α induced cPLA2 mRNA and protein expression, promoter activity, and PGE2 secretion in HPAEpiCs. These responses induced by TNF-α were inhibited by pretreatment with the inhibitor of Jak2 (AG490), platelet-derived growth factor receptor (PDGFR) (AG1296), phosphoinositide 3 kinase (PI3K) (LY294002), or MEK1/2 (PD98059) and transfection with siRNA of Jak2, PDGFR, Akt, or p42. We showed that TNF-α markedly stimulated Jak2, PDGFR, Akt, and p42/p44 MAPK phosphorylation, which were attenuated by their respective inhibitors. Moreover, TNF-α stimulated Akt activation via a Jak2/PDGFR pathway in HPAEpiCs. In addition, TNF-α-induced p42/p44 MAPK phosphorylation was reduced by AG1296 or LY294002. On the other hand, TNF-α could induce Akt and p42/p44 MAPK translocation from the cytosol into the nucleus, which was inhibited by AG490, AG1296, or LY294002. Finally, we showed that TNF-α stimulated Elk-1 phosphorylation, which was reduced by LY294002 or PD98059. We also observed that TNF-α time dependently induced p300/Elk-1 and p300/Akt complex formation in HPAEpiCs, which was reduced by AG490, AG1296, or LY294002. The activity of cPLA2 protein upregulated by TNF-α was reflected on the PGE2 release, which was reduced by AG490, AG1296, LY294002 , or PD98059. Taken together, these results demonstrated that TNF-α-induced cPLA2 expression and PGE2 release were mediated through a Jak2/PDGFR/PI3K/Akt/p42/p44 MAPK/Elk-1 pathway in HPAEpiCs.

Cytoskeletal architecture in mouse lung epithelial cells is regulated by protein-kinase C-alpha and calpain II

1996 ◽  
Vol 270 (4) ◽  
pp. L526-L534 ◽  
Author(s):  
L. D. Dwyer-Nield ◽  
A. C. Miller ◽  
B. W. Neighbors ◽  
D. Dinsdale ◽  
A. M. Malkinson
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Actin Stress Fiber ◽  
Kinase C ◽  
Lung Epithelial ◽  
Pkc Alpha ◽  
Calpain Ii

Brief exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA) caused a uniformly flattened population of mouse lung epithelial cells to become more heterogeneous; some cells rounded up, and others detached to overlap with flatter cells. Actin stress fiber organization was disrupted, and F-actin accumulated in lemellipodia. Vinculin dissociated from the focal adhesion plaques to diffuse throughout the cytoplasm. Inhibition of protein kinase C (PKC) activity blocked these effects of TPA. After 8 h of TPA exposure, actin filaments reassembled and vinculin again localized to the cell periphery. Calpain inhibition attenuated the decrease of PKC-alpha protein and PKC activity from the membrane fraction, and prevented the redistribution of cytoskeletal elements. Talin immunostaining was widespread throughout control cells but was localized to the periphery 8 h after treatment with TPA or with inhibitors of PKC and calpain. Both vinculin and talin concentrations increased with prolonged TPA treatment. PKC-zeta and calpain II were not appreciably affected by TPA exposure. Translocation of PKC-alpha to the membrane, followed by its calpain-induced downmodulation, is apparently required for the reversible pattern of cytoskeletal changes caused by TPA.

scholarly journals Peptidome analysis of umbilical cord mesenchymal stem cell (hUC-MSC) conditioned medium from preterm and term infants

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Wang ◽  
Lin Zhang ◽  
Yun Wu ◽  
Rongping Zhu ◽  
Yan Wang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Lung ◽  
Lung Epithelial Cells ◽  
Differentially Expressed ◽  
Tandem Mass ◽  
Tnf Α ◽  
Lung Epithelial ◽  
Precursor Proteins ◽  
Human Lung Epithelial Cells

Abstract Background The therapeutic role of mesenchymal stem cells (MSCs) has been widely confirmed in several animal models of premature infant diseases. Micromolecule peptides have shown promise for the treatment of premature infant diseases. However, the potential role of peptides secreted from MSCs has not been studied. The purpose of this study is to help to broaden the knowledge of the hUC-MSC secretome at the peptide level through peptidomic profile analysis. Methods We used tandem mass tag (TMT) labeling technology followed by tandem mass spectrometry to compare the peptidomic profile of preterm and term umbilical cord MSC (hUC-MSC) conditioned medium (CM). Gene Ontology (GO) enrichment analysis and ingenuity pathway analysis (IPA) were conducted to explore the differentially expressed peptides by predicting the functions of their precursor proteins. To evaluate the effect of candidate peptides on human lung epithelial cells stimulated by hydrogen peroxide (H2O2), quantitative real-time PCR (qRT-PCR), western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were, respectively, adopted to detect inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression levels at the mRNA and protein levels. Results A total of 131 peptides derived from 106 precursor proteins were differentially expressed in the preterm hUC-MSC CM compared with the term group, comprising 37 upregulated peptides and 94 downregulated peptides. Bioinformatics analysis showed that these differentially expressed peptides may be associated with developmental disorders, inflammatory response, and organismal injury. We also found that peptides 7118TGAKIKLVGT7127 derived from MUC19 and 508AAAAGPANVH517 derived from SIX5 reduced the expression levels of TNF-α, IL-1β, and IL-6 in H2O2-treated human lung epithelial cells. Conclusions In summary, this study provides further secretomics information on hUC-MSCs and provides a series of peptides that might have antiinflammatory effects on pulmonary epithelial cells and contribute to the prevention and treatment of respiratory diseases in premature infants.

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