DOI: 10.4049/jimmunol.161.6.3120. CD40-Mediated Signal Transduction in Human Airway Smooth Muscle [Penn]

CD40-Mediated Signal Transduction in Human Airway Smooth Muscle

10.4049/jimmunol.161.6.3120

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

AbstractCD40 is a member of the TNF receptor family that was initially described on the surface of B cells. Recently, CD40 has also been described on mesenchymal cells, such as endothelial cells and fibroblasts, where engagement by its ligand CD40 ligand can lead to up-regulation of costimulatory and cell adhesion molecules, as well as secretion of proinflammatory cytokines. Since airway inflammation potentially involves cell-cell interactions of T cells and eosinophils (which express CD40 ligand) with airway smooth muscle (ASM) cells, we postulated that ASM may express CD40 and that engagement of ASM CD40 may modulate smooth muscle cell function. We demonstrate that CD40 is expressed on cultured human ASM and that expression can be increased by treatment with TNF-α or IFN-γ. Cross-linking CD40 on ASM resulted in enhanced IL-6 secretion and an increase in intracellular calcium concentrations, which were dependent on calcium influx. We show that CD40-mediated signaling events include protein tyrosine phosphorylation and activation of NF-κB. Pretreatment of ASM with the tyrosine kinase inhibitors genistein or herbimycin inhibited the rapid mobilization of calcium induced via CD40, suggesting that calcium mobilization was coupled to activation of protein tyrosine kinases. In addition, inhibition of calcium influx inhibited both CD40-mediated NF-κB activation and enhancement of IL-6 secretion. These results delineate a potentially important CD40-mediated signal-transduction pathway in ASM, involving protein tyrosine kinase-dependent calcium mobilization, NF-κB activation, and IL-6 production. Together, these results suggest a mechanism whereby T cell/smooth muscle cell interactions may potentiate airway inflammation.

Bibliography

Lazaar, A. L., Amrani, Y., Hsu, J., Panettieri, R. A., Fanslow, W. C., Albelda, S. M., & PureÌ, E. (1998). CD40-Mediated Signal Transduction in Human Airway Smooth Muscle. The Journal of Immunology, 161(6), 3120â3127.

Authors 7

Aili L. Lazaar (first)
Yassine Amrani (additional)
Jason Hsu (additional)
Reynold A. Panettieri (additional)
William C. Fanslow (additional)
Steven M. Albelda (additional)
Ellen Puré (additional)

References 58 Referenced 67

Dates

Type	When
Created	2 years, 8 months ago (Dec. 31, 2022, 9:38 a.m.)
Deposited	8 months ago (Jan. 2, 2025, 12:46 p.m.)
Indexed	8 months ago (Jan. 3, 2025, 12:31 a.m.)
Issued	26 years, 11 months ago (Sept. 15, 1998)
Published	26 years, 11 months ago (Sept. 15, 1998)
Published Print	26 years, 11 months ago (Sept. 15, 1998)

Funders 0

None

BibTeX

@article{Lazaar_1998, title={CD40-Mediated Signal Transduction in Human Airway Smooth Muscle}, volume={161}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.161.6.3120}, DOI={10.4049/jimmunol.161.6.3120}, number={6}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Lazaar, Aili L. and Amrani, Yassine and Hsu, Jason and Panettieri, Reynold A. and Fanslow, William C. and Albelda, Steven M. and Puré, Ellen}, year={1998}, month=sep, pages={3120–3127} }

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  "abstract": "<jats:title>Abstract</jats:title><jats:p>CD40 is a member of the TNF receptor family that was initially described on the surface of B cells. Recently, CD40 has also been described on mesenchymal cells, such as endothelial cells and fibroblasts, where engagement by its ligand CD40 ligand can lead to up-regulation of costimulatory and cell adhesion molecules, as well as secretion of proinflammatory cytokines. Since airway inflammation potentially involves cell-cell interactions of T cells and eosinophils (which express CD40 ligand) with airway smooth muscle (ASM) cells, we postulated that ASM may express CD40 and that engagement of ASM CD40 may modulate smooth muscle cell function. We demonstrate that CD40 is expressed on cultured human ASM and that expression can be increased by treatment with TNF-\u03b1 or IFN-\u03b3. Cross-linking CD40 on ASM resulted in enhanced IL-6 secretion and an increase in intracellular calcium concentrations, which were dependent on calcium influx. We show that CD40-mediated signaling events include protein tyrosine phosphorylation and activation of NF-\u03baB. Pretreatment of ASM with the tyrosine kinase inhibitors genistein or herbimycin inhibited the rapid mobilization of calcium induced via CD40, suggesting that calcium mobilization was coupled to activation of protein tyrosine kinases. In addition, inhibition of calcium influx inhibited both CD40-mediated NF-\u03baB activation and enhancement of IL-6 secretion. These results delineate a potentially important CD40-mediated signal-transduction pathway in ASM, involving protein tyrosine kinase-dependent calcium mobilization, NF-\u03baB activation, and IL-6 production. Together, these results suggest a mechanism whereby T cell/smooth muscle cell interactions may potentiate airway inflammation.</jats:p>",
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