CD40-mediated signal transduction in human airway smooth muscle

Aili L. Lazaar, Yassine Amrani, Jason Hsu, Reynold Panettieri, William C. Fanslow, Steven M. Albelda, Ellen Puré

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

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-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.

Original languageEnglish (US)
Pages (from-to)3120-3127
Number of pages8
JournalJournal of Immunology
Volume161
Issue number6
StatePublished - Sep 15 1998
Externally publishedYes

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Smooth Muscle
Signal Transduction
Calcium
Protein-Tyrosine Kinases
Smooth Muscle Myocytes
Interleukin-6
CD40 Ligand
Cell Communication
Inflammation
T-Lymphocytes
Muscle Proteins
Genistein
Tumor Necrosis Factor Receptors
Cell Adhesion Molecules
Eosinophils
Tyrosine
B-Lymphocytes
Up-Regulation
Endothelial Cells
Fibroblasts

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Lazaar, A. L., Amrani, Y., Hsu, J., Panettieri, R., Fanslow, W. C., Albelda, S. M., & Puré, E. (1998). CD40-mediated signal transduction in human airway smooth muscle. Journal of Immunology, 161(6), 3120-3127.
Lazaar, Aili L. ; Amrani, Yassine ; Hsu, Jason ; Panettieri, Reynold ; Fanslow, William C. ; Albelda, Steven M. ; Puré, Ellen. / CD40-mediated signal transduction in human airway smooth muscle. In: Journal of Immunology. 1998 ; Vol. 161, No. 6. pp. 3120-3127.
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Lazaar, AL, Amrani, Y, Hsu, J, Panettieri, R, Fanslow, WC, Albelda, SM & Puré, E 1998, 'CD40-mediated signal transduction in human airway smooth muscle', Journal of Immunology, vol. 161, no. 6, pp. 3120-3127.

CD40-mediated signal transduction in human airway smooth muscle. / Lazaar, Aili L.; Amrani, Yassine; Hsu, Jason; Panettieri, Reynold; Fanslow, William C.; Albelda, Steven M.; Puré, Ellen.

In: Journal of Immunology, Vol. 161, No. 6, 15.09.1998, p. 3120-3127.

Research output: Contribution to journalArticle

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AU - Lazaar, Aili L.

AU - Amrani, Yassine

AU - Hsu, Jason

AU - Panettieri, Reynold

AU - Fanslow, William C.

AU - Albelda, Steven M.

AU - Puré, Ellen

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Lazaar AL, Amrani Y, Hsu J, Panettieri R, Fanslow WC, Albelda SM et al. CD40-mediated signal transduction in human airway smooth muscle. Journal of Immunology. 1998 Sep 15;161(6):3120-3127.