Back to Search
Start Over
CD40 on adult human airway epithelial cells: expression and proinflammatory effects.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 Mar 01; Vol. 172 (5), pp. 3205-14. - Publication Year :
- 2004
-
Abstract
- CD40/CD40 ligand interaction is an important pathway for B and T cell cooperation and function; functional CD40 molecules have recently been found on nonhematopoietic cells. We detected CD40 in vivo on normal human respiratory epithelial cells and showed that its expression is increased on inflamed airway epithelium. Subsequently, we analyzed its expression and function on primary cultures of human airway epithelial cells. Our data show that CD40 is up-regulated by IFN-beta and IFN-gamma, its ligation increases the surface expression of CD54 and CD106 and it may stimulate the release of IL-6 and IL-8. The use of Janus kinase 3 (JAK3) and NF-kappaB inhibitors suggests that both basal and CD40-induced release of the two cytokines is JAK3-dependent. Using colocalization techniques, we revealed the existence of CD40/JAK3 and CD40/TNFR-associated factor 2 interplay. The extent of these interactions may be partial (2-40% of the cells) or massive (80-90% of the cells) in cultured cells. Stimulation via CD40 causes a significant increase in the number of cells expressing colocalization only in the cultures displaying low frequency of initial colocalization. Thus, airway epithelial cells, activated by CD40, may behave as effector cells of the inflammation process and should be considered priority targets for anti-inflammatory therapy. This work identifies CD40 and the correlated JAK3 signaling molecule as potential molecular targets to block the inflammatory functions of epithelial cells.
- Subjects :
- Adult
Aged
Asthma immunology
Asthma pathology
CD40 Antigens immunology
CD40 Antigens metabolism
CD40 Ligand metabolism
CD40 Ligand physiology
Cell Line
Female
Humans
Immunoglobulin M metabolism
Immunohistochemistry
Inflammation Mediators immunology
Janus Kinase 3
Ligands
Male
Middle Aged
Protein-Tyrosine Kinases metabolism
Protein-Tyrosine Kinases physiology
Proteins physiology
Receptors, Tumor Necrosis Factor physiology
Respiratory Mucosa enzymology
Respiratory Mucosa metabolism
Signal Transduction immunology
TNF Receptor-Associated Factor 2
CD40 Antigens biosynthesis
CD40 Antigens physiology
Inflammation Mediators metabolism
Inflammation Mediators physiology
Respiratory Mucosa immunology
Respiratory Mucosa pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 172
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 14978128
- Full Text :
- https://doi.org/10.4049/jimmunol.172.5.3205