scholarly journals Mycoplasma fermentansand TNF-β interact to amplify immune-modulating cytokines in human lung fibroblasts

2006 ◽  
Vol 291 (4) ◽  
pp. L781-L793 ◽  
Author(s):  
James P. Fabisiak ◽  
Fei Gao ◽  
Robyn G. Thomson ◽  
Robert M. Strieter ◽  
Simon C. Watkins ◽  
...  
Keyword(s):  
Protein Kinase ◽  
In Vitro Model ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Mycoplasma Fermentans ◽  
Human Lung Fibroblasts ◽  
Toll Like Receptor 2 ◽  
Vitro Model ◽  
Specific Ligand

Mycoplasma can establish latent infections and are associated with arthritis, leukemia, and chronic lung disease. We developed an experimental model in which lung cells are deliberately infected with Mycoplasma fermentans. Human lung fibroblasts (HLF) were exposed to live M. fermentans and immune-modulating cytokine release was assessed with and without known inducers of cytokine production. M. fermentans increased IL-6, IL-8/CXCL8, MCP-1/CCL2, and Gro-α/CXCL1 production. M. fermentans interacted with TNF-β to release more IL-6, CXCL8, and CXCL1 than predicted by the responses to either stimulus alone. The effects of live infection were recapitulated by exposure to M. fermentans-derived macrophage-activating lipopeptide-2 (MALP-2), a Toll-like receptor-2- and receptor-6-specific ligand. The synergistic effect of combined stimuli was more pronounced with prolonged incubations. Preexposure to TNF-β sensitized the cells to subsequent MALP-2 challenge, but preexposure to MALP-2 did not alter the IL-6 response to TNF-β. Exposure to M. fermentans or MALP-2 did not enhance nuclear localization, DNA binding, or transcriptional activity of NF-κB and did not modulate early NF-κB activation in response to TNF-β. Application of specific inhibitors of various MAPKs suggested that p38 and JNK/stress-activated protein kinase were involved in early IL-6 release after exposure to TNF-β and M. fermentans, respectively. The combined response to M. fermentans and TNF-β, however, was uniquely sensitive to delayed application of SP-600125, suggesting that JNK/stress-activated protein kinase contributes to the amplification of IL-6 release. Thus M. fermentans interacts with stimuli such as TNF-β to amplify lung cell production of immune-modulating cytokines. The mechanisms accounting for this interaction can now be dissected with the use of this in vitro model.

scholarly journals Interaction of Mycoplasma pneumoniae with human lung fibroblasts: characterization of the in vitro model.

1979 ◽  
Vol 25 (1) ◽  
pp. 446-454 ◽  
Author(s):  
M G Gabridge ◽  
D Taylor-Robinson ◽  
H A Davies ◽  
R R Dourmashkin
Keyword(s):  
Mycoplasma Pneumoniae ◽  
In Vitro Model ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Vitro Model

scholarly journals Fenofibrate inhibits TGF‐β‐induced myofibroblast differentiation and activation in human lung fibroblasts in vitro

FEBS Open Bio ◽  
2021 ◽  
Author(s):  
Ryota Kikuchi ◽  
Yuki Maeda ◽  
Takao Tsuji ◽  
Kazuhiro Yamaguchi ◽  
Shinji Abe ◽  
...  
Keyword(s):  
Human Lung ◽  
Lung Fibroblasts ◽  
Myofibroblast Differentiation ◽  
Human Lung Fibroblasts

scholarly journals Multiple protein kinase pathways mediate amplified IL-6 release by human lung fibroblasts co-exposed to nickel and TLR-2 agonist, MALP-2

2010 ◽  
Vol 247 (2) ◽  
pp. 146-157 ◽  
Author(s):  
Fei Gao ◽  
Kelly A. Brant ◽  
Rachel M. Ward ◽  
Richard T. Cattley ◽  
Aaron Barchowsky ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Multiple Protein

scholarly journals Silver Nanoparticles Alter Cell Viability Ex Vivo and in Vitro and Induce Proinflammatory Effects in Human Lung Fibroblasts

Nanomaterials ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1868
Author(s):  
Anna Löfdahl ◽  
Andreas Jern ◽  
Samuel Flyman ◽  
Monica Kåredal ◽  
Hanna L Karlsson ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Cell Viability ◽  
Human Lung ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Metabolic Activities ◽  
Precision Cut Lung Slices

Silver nanoparticles (AgNPs) are commonly used in commercial and medical applications. However, AgNPs may induce toxicity, extracellular matrix (ECM) changes and inflammatory responses. Fibroblasts are key players in remodeling processes and major producers of the ECM. The aims of this study were to explore the effect of AgNPs on cell viability, both ex vivo in murine precision cut lung slices (PCLS) and in vitro in human lung fibroblasts (HFL-1), and immunomodulatory responses in fibroblasts. PCLS and HFL-1 were exposed to AgNPs with different sizes, 10 nm and 75 nm, at concentrations 2 µg/mL and 10 μg/mL. Changes in synthesis of ECM proteins, growth factors and cytokines were analyzed in HFL-1. Ag10 and Ag75 affected cell viability, with significantly reduced metabolic activities at 10 μg/mL in both PCLS and HFL-1 after 48 h. AgNPs significantly increased procollagen I synthesis and release of IL-8, prostaglandin E2, RANTES and eotaxin, whereas reduced IL-6 release was observed in HFL-1 after 72 h. Our data indicate toxic effects of AgNP exposure on cell viability ex vivo and in vitro with altered procollagen and proinflammatory cytokine secretion in fibroblasts over time. Hence, careful characterizations of AgNPs are of importance, and future studies should include timepoints beyond 24 h.

scholarly journals Human lung fibroblasts may modulate dendritic cell phenotype and function: results from a pilot in vitro study

2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Olivia Freynet ◽  
Joëlle Marchal-Sommé ◽  
Francette Jean-Louis ◽  
Arnaud Mailleux ◽  
Bruno Crestani ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Human Lung ◽  
In Vitro Study ◽  
Vitro Study ◽  
Lung Fibroblasts ◽  
Cell Phenotype ◽  
Human Lung Fibroblasts ◽  
And Function

scholarly journals Peroxisome proliferator-activated receptor-γ ligands induce heme oxygenase-1 in lung fibroblasts by a PPARγ-independent, glutathione-dependent mechanism

2009 ◽  
Vol 297 (5) ◽  
pp. L912-L919 ◽  
Author(s):  
Heather E. Ferguson ◽  
Thomas H. Thatcher ◽  
Keith C. Olsen ◽  
Tatiana M. Garcia-Bates ◽  
Carolyn J. Baglole ◽  
...  
Keyword(s):  
Human Lung ◽  
Lung Fibroblasts ◽  
Heme Oxygenase 1 ◽  
Peroxisome Proliferator ◽  
Covalent Bonds ◽  
Peroxisome Proliferator Activated Receptor ◽  
Human Lung Fibroblasts ◽  
Thiol Antioxidant ◽  
Dependent Mechanism

Oxidative stress plays an important role in the pathogenesis of pulmonary fibrosis. Heme oxygenase-1 (HO-1) is a key antioxidant enzyme, and overexpression of HO-1 significantly decreases lung inflammation and fibrosis in animal models. Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor that regulates adipogenesis, insulin sensitization, and inflammation. We report here that the PPARγ ligands 15d-PGJ2 and 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), which have potent antifibrotic effects in vitro, also strongly induce HO-1 expression in primary human lung fibroblasts. Pharmacological and genetic approaches are used to demonstrate that induction of HO-1 is PPARγ independent. Upregulation of HO-1 coincides with decreased intracellular glutathione (GSH) levels and can be inhibited by N-acetyl cysteine (NAC), a thiol antioxidant and GSH precursor. Upregulation of HO-1 is not inhibited by Trolox, a non-thiol antioxidant, and does not involve the transcription factors AP-1 or Nrf2. CDDO and 15d-PGJ2 contain an α/β unsaturated ketone that acts as an electrophilic center that can form covalent bonds with free reduced thiols. Rosiglitazone, a PPARγ ligand that lacks an electrophilic center, does not induce HO-1. These data suggest that in human lung fibroblasts, 15d-PGJ2 and CDDO induce HO-1 via a GSH-dependent mechanism involving the formation of covalent bonds between 15d-PGJ2 or CDDO and GSH. Inhibiting HO-1 upregulation with NAC has only a small effect on the antifibrotic properties of 15d-PGJ2 and CDDO in vitro. These results suggest that CDDO and similar electrophilic PPARγ ligands may have great clinical potential as antifibrotic agents, not only through direct effects on fibroblast differentiation and function, but indirectly by bolstering antioxidant defenses.

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