Essential role of IFNβ and CD38 in TNFα-induced airway smooth muscle hyper-responsiveness

Deepika Jain, Stefan Keslacy, Omar Tliba, Yang Cao, Sonja Kierstein, Kunjlata Amin, Reynold A. Panettieri, Angela Franciska Haczku, Yassine Amrani

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

We recently identified autocrine interferon (IFN)β as a novel mechanism mediating tumor necrosis factor (TNF)α-induced expression of inflammatory genes in airway smooth muscle (ASM) cells, including CD38, known to regulate calcium signaling. Here, we investigated the putative involvement of IFNβ in regulating TNFα-induced airway hyper-responsiveness (AHR), a defining feature of asthma. Using our pharmacodynamic model to assess ex vivo AHR isolated murine tracheal rings, we found that TNFα-induced enhanced contractile responses to carbachol and bradykinin was abrogated by neutralizing anti-IFNβ antibody or in tracheal rings deficient in CD38. In cultured human ASM cells, where CD38 has been involved in TNFα-induced enhanced calcium signals to carbachol and bradykinin, we found that neutralizing anti-IFNβ prevented TNFα enhancing action only on carbachol responses but not to that induced by bradykinin. In a well-characterized model of allergic asthma (mice sensitized and challenged with Aspergillus fumigatus (Af)), we found heightened expression of both IFNβ and CD38 in the airways. Furthermore, allergen-associated AHR to methacholine, assessed by lung resistance and dynamic compliance, was completely suppressed in CD38-deficient mice, despite the preservation of airway inflammation. These data provide the first evidence that ASM-derived IFNβ and CD38 may play a significant role in the development of TNFα-associated AHR.

Original languageEnglish (US)
Pages (from-to)499-509
Number of pages11
JournalImmunobiology
Volume213
Issue number6
DOIs
StatePublished - Jul 10 2008
Externally publishedYes

Fingerprint

Respiratory Hypersensitivity
Interferons
Smooth Muscle
Tumor Necrosis Factor-alpha
Carbachol
Bradykinin
Smooth Muscle Myocytes
Asthma
Aspergillus fumigatus
Calcium Signaling
Methacholine Chloride
Neutralizing Antibodies
Allergens
Compliance
Anti-Idiotypic Antibodies
Inflammation
Calcium
Gene Expression
Lung

Keywords

  • Airway smooth muscle
  • Allergic asthma
  • Calcium signaling
  • Cytokine
  • Hypercontractility
  • Inflammation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Hematology

Cite this

Jain, D., Keslacy, S., Tliba, O., Cao, Y., Kierstein, S., Amin, K., ... Amrani, Y. (2008). Essential role of IFNβ and CD38 in TNFα-induced airway smooth muscle hyper-responsiveness. Immunobiology, 213(6), 499-509. https://doi.org/10.1016/j.imbio.2007.12.002

Essential role of IFNβ and CD38 in TNFα-induced airway smooth muscle hyper-responsiveness. / Jain, Deepika; Keslacy, Stefan; Tliba, Omar; Cao, Yang; Kierstein, Sonja; Amin, Kunjlata; Panettieri, Reynold A.; Haczku, Angela Franciska; Amrani, Yassine.

In: Immunobiology, Vol. 213, No. 6, 10.07.2008, p. 499-509.

Research output: Contribution to journalArticle

Jain, D, Keslacy, S, Tliba, O, Cao, Y, Kierstein, S, Amin, K, Panettieri, RA, Haczku, AF & Amrani, Y 2008, 'Essential role of IFNβ and CD38 in TNFα-induced airway smooth muscle hyper-responsiveness', Immunobiology, vol. 213, no. 6, pp. 499-509. https://doi.org/10.1016/j.imbio.2007.12.002
Jain, Deepika ; Keslacy, Stefan ; Tliba, Omar ; Cao, Yang ; Kierstein, Sonja ; Amin, Kunjlata ; Panettieri, Reynold A. ; Haczku, Angela Franciska ; Amrani, Yassine. / Essential role of IFNβ and CD38 in TNFα-induced airway smooth muscle hyper-responsiveness. In: Immunobiology. 2008 ; Vol. 213, No. 6. pp. 499-509.
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