Role of CD38 in TNF-α-induced airway hyperresponsiveness

Alonso G.P. Guedes, Joseph A. Jude, Jaime Paulin, Hirohito Kita, Frances E. Lund, Mathur S. Kannan

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


CD38 is involved in normal airway function, IL-13-induced airway hyperresponsiveness (AHR), and is also regulated by tumor necrosis factor (TNF)-α in airway smooth muscle (ASM) cells. This study aimed to determine whether TNF-α-induced CD38 upregulation in ASM cells contributes to AHR, a hallmark of asthma. We hypothesized that AHR would be attenuated in TNF-α-exposed CD38-deficient (CD38KO) mice compared with wild-type (WT) controls. Mice (n = 6-8/group) were intranasally challenged with vehicle control or TNF-α (50 ng) once and every other day during 1 or 4 wk. Lung inflammation and AHR, measured by changes in lung resistance after inhaled methacholine, were assessed 24 h following the last challenge. Tracheal rings were incubated with TNF-α (50 ng/ml) to assess contractile changes in the ASM. While a single TNF-α challenge caused no airway inflammation, both multiple-challenge protocols induced equally significant inflammation in CD38KO and WT mice. A single intranasal TNF-α challenge induced AHR in the WT but not in the CD38KO mice, whereas both mice developed AHR after 1 wk of challenges. The AHR was suppressed by extending the challenges for 4 wk in both mice, although to a larger magnitude in the WT than in the CD38KO mice. TNF-α increased ASM contractile properties in tracheal rings from WT but not from CD38KO mice. In conclusion, CD38 contributes to TNF-α-induced AHR after a brief airway exposure to the cytokine, likely by mediating changes in ASM contractile responses, and is associated with greater AHR remission following chronic airway exposure to TNF-α. The mechanisms involved in this remission remain to be determined.

Original languageEnglish (US)
Pages (from-to)L290-L299
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number2
StatePublished - Feb 2008


  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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