Constitutive and inducible thymic stromal lymphopoietin expression in human airway smooth muscle cells: role in chronic obstructive pulmonary disease

Am J Physiol Lung Cell Mol Physiol. 2007 Aug;293(2):L375-82. doi: 10.1152/ajplung.00045.2007. Epub 2007 May 18.

Abstract

Thymic stromal lymphopoietin (TSLP) is a novel cytokine that triggers dendritic cell-mediated T helper (Th)-2 inflammatory responses. Previous studies have demonstrated that human airway smooth muscle cells (HASMC) play a critical role in initiating or perpetuating airway inflammation by producing chemokines and cytokines. In this study, we first evaluated the expression of TSLP in primary HASMC and investigated how proinflammatory cytokines (TNF-alpha and IL-1beta) and Th-2 cytokines (IL-4, IL-9) regulate TSLP production from HASMC. TSLP mRNA and protein were assessed by real-time RT-PCR, ELISA, and immunofluorescence from primary HASMC cultures. Primary HASMC express constitutive level of TSLP. Incubation of HASMC with IL-1 or TNF-alpha resulted in a significant increase of TSLP mRNA and protein release from HASMC. Furthermore, combination of IL-1beta and TNF-alpha has an additive effect on TSLP release by HASMC. Primary HASMC pretreated with inhibitors of p38 or p42/p44 ERK MAPK, but not phosphatidylinositol 3-kinase, showed a significant decrease in TSLP release on IL-1beta and TNF-alpha treatment. Furthermore, TSLP immunoreactivity was present in ASM bundle from chronic obstructive pulmonary disease (COPD) and to lesser degree in normal subjects. Taken together, our data provide the first evidence of IL-1beta- and TNF-alpha-induced TSLP expression in HASMC via (p38, p42/p44) MAPK signaling pathways. Our results raise the possibility that HASMC may play a role in COPD airway inflammation via TSLP-dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchi / cytology*
  • Cells, Cultured
  • Cytokines / genetics*
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Humans
  • Interleukin-1beta / pharmacology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / immunology
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / immunology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pneumonia / immunology
  • Pneumonia / physiopathology
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Cytokines
  • Interleukin-1beta
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • thymic stromal lymphopoietin