Title :

Potent synergistic effect of IL-3 and TNF on matrix metalloproteinase 9 generation by human eosinophils.

Author(s) :

Kelly, Elizabeth A B [Auteur]
University of Wisconsin School of Medicine and Public Health
Liu, Lin Ying [Auteur]
University of Wisconsin School of Medicine and Public Health
Esnault, Stéphane [Auteur]
University of Wisconsin School of Medicine and Public Health
Quinchia Johnson, Beatriz Helena [Auteur]
University of Wisconsin School of Medicine and Public Health
Jarjour, Nizar N [Auteur]
University of Wisconsin School of Medicine and Public Health

Journal title :

Cytokine

Volume number :

58

Pages :

199-206

Publication date :

2012-05-01

ISSN :

1096-0023

English keyword(s) :

Cytokines
Enzyme-Linked Immunosorbent Assay
Eosinophils
Extracellular Signal-Regulated MAP Kinases
Flow Cytometry
Humans
Interleukin-3
Matrix Metalloproteinase 9
Phosphorylation
RNA, Messenger
Real-Time Polymerase Chain Reaction
Tumor Necrosis Factor-alpha

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

TNF (designated as TNF-α under previous nomenclature) is the preeminent activator of MMP-9 generation from a variety of cells including eosinophils. We have previously established that TNF strongly synergizes with IFN-γ ...
Show more >TNF (designated as TNF-α under previous nomenclature) is the preeminent activator of MMP-9 generation from a variety of cells including eosinophils. We have previously established that TNF strongly synergizes with IFN-γ and IL-4 for eosinophil synthesis of Th1- and Th2-type chemokines respectively. Thus, we sought to determine if TNF-induced synthesis of MMP-9 would be enhanced by the presence of Th1, Th2, or the eosinophil-associated common beta chain (βc) cytokines. Human blood eosinophils were cultured with TNF alone or in combination with either IFN-γ, IL-4, IL-3, IL-5, or GM-CSF. Concentrations and activities of MMP-9 in eosinophil culture supernates were measured by ELISA and gelatin zymography, mRNA transcription and stabilization by quantitative real-time PCR, and signaling events by immunoblotting and intracellular flow cytometric analysis. Individually, TNF, GM-CSF, or IL-3, but not IL-4 or IFN-γ, induced relatively small (GM-CSF>IL-5. Zymography revealed that eosinophils release MMP-9 in its pro-form. Eosinophil stimulation with the combination of IL-3 plus TNF led to increased steady-state levels of MMP-9 mRNA, prolonged mRNA stabilization, and enhanced activation of ERK1/2 phosphorylation. Inhibition of NF-κB, MEK kinase, or p38 MAP kinase, but not JNK signaling pathways, diminished IL-3/TNF-induced MMP-9 mRNA and protein production. Thus, the synergistic regulation of eosinophil MMP-9 by IL-3 plus TNF likely involves cooperative interaction of multiple transcription factors downstream from ERK, p38, and NF-κB activation as well as post-transcriptional regulation of MMP-9 mRNA stabilization. Our data indicate that within microenvironments rich in βc-family cytokines and TNF, eosinophils are an important source of proMMP-9 and highlight a previously unrecognized role for synergistic interaction between TNF and βc-family cytokines, particularly IL-3, for proMMP-9 synthesis.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Autres travaux scientifiques

Submission date :

2023-11-14T10:40:50Z
2024-03-18T09:01:11Z