Abstract: Poster Presentations |

Suppression of Dendritic Cell Inducibe Co-stimulatory Molecule Expression and IL-12 Secretion by Cigarette Smoke Extract FREE TO VIEW

Robert Vassallo, MD; Lieping Chen, MD, PhD
Author and Funding Information

Mayo Clinic, Rochester, MN


Chest. 2003;124(4_MeetingAbstracts):135S. doi:10.1378/chest.124.4_MeetingAbstracts.135S-a
Text Size: A A A
Published online


PURPOSE:  Dendritic cells are present in the lung in an immature state. Upon encounter with antigen or inflammatory stimuli, dendritic cells undergo maturation, a process associated with up-regulation of costimulatory molecules and secretion of IL-12. This process confers to the dendritic cell enhanced capacity to stimulate T cell responses. We speculated that cigarette smoking impairs the ability of dendritic cells to undergo maturation, thereby inhibiting their ability to stimulate T cell responses.

METHODS:  Immature dendritic cells were generated from monoyctes cultured with interleukin-4 (5ng/ml) and GM-CSF (800U/ml). Mature dendritic cells were generated by the addition of lipopolysaccharide (LPS, 100ng/ml) in the final 24 hours of culture. Cigarette smoke extract (CSE) was generated from cigarettes by bubbling mainstream cigarettes smoke from one cigarette into 10ml media (nicotine concentration of 2.3±0.8 microg/mL in 1% CSE). Costimulatory molecule expression was determined by flow cytometry. Dendritic cell interleukin-12 (IL-12) and interleukin-6 (IL-6) production were determined by ELISA.

RESULTS:  Although CSE did not alter the expression of CD-40, CD-80, CD-86, and CD1a expression on resting immature dendritic cells, CSE (1-2%) caused significant suppression of LPS-induced upregulation of these co-stimulatory molecules. In contrast, nicotine (1-100 micrograms/ml) had no effect on resting or inducible co-stimulatory molecule expression. CSE also potently inhibited LPS-induced IL-12 secretion: whereas LPS-stimulated dendritic cells produced 1052 ± 9 pg/ml IL-12, LPS-stimulated dendritic cells in the presence of 2% CSE produced only 340 ± 9 pg/ml (p<0.01). In contrast to the suppressive effect on IL-12 secretion, CSE did not alter LPS-induced secretion of IL-6 by dendritic cells.CONCLUSIONS: These data indicate that CSE suppress specific dendritic cell functions that are important in host responses to infection and cancer. Through these effects on dendritic cell function, cigarette smoke components may alter adaptive immune responses.

CLINICAL IMPLICATIONS:  These findings have important implications for the pathogenesis of disease states associated with smoking.

DISCLOSURE:  R. Vassallo, None.

Wednesday, October 29, 2003

12:30 PM- 2:00 PM




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
Myristoylated Alanine-Rich C-Kinase Substrate Protein*: A Major Intracellular Regulatory Molecule Controlling Secretion of Mucin by Human Airway Goblet Cells
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543