Format

Send to

Choose Destination
See comment in PubMed Commons below
Laryngoscope. 2013 Sep;123(9):2228-36. doi: 10.1002/lary.24052. Epub 2013 Mar 13.

Paracrine potential of fibroblasts exposed to cigarette smoke extract with vascular growth factor induction.

Author information

1
Department of Surgery, University of Wisconsin, Madison, Wisconsin, U.S.A.

Abstract

OBJECTIVES/HYPOTHESIS:

Nicotine, a major constituent of cigarette smoke, can activate the cholinergic anti-inflammatory pathway by binding to α7-nicotinic acetylcholine receptor (α7nAChR) expressed on the surface of certain cells. Here, we ask whether cigarette smoke extract induced different paracrine factors compared to the in vivo regulator of inflammation, tumor necrosis factor-α, in human vocal fold fibroblasts (hVFFs) shown to express low levels of α7nAChR.

STUDY DESIGN:

In vitro.

METHODS:

α7nAChR was detected by nested polymerase chain reaction and immunohistochemistry. γH2AX, a marker for DNA double-stand breaks, was measured by immunofluorescence. Cigarette smoke extract was prepared in accordance with investigators studying effects of cigarette smoke. hVFFs treated for 3 hours had media replaced for an additional 24 hours. Cytokine, chemokine, and growth factor levels in media were assessed by multiplex analysis.

RESULTS:

α7nAChR expression levels decreased with the passage number of fibroblasts. Tumor necrosis factor-α induced a significantly different profile of cytokines, chemokines, and growth factor compared to cigarette smoke extract exposure. Cigarette smoke extract at a concentration not associated with induction of γH2AX nuclear foci significantly increased vascular endothelial growth factor.

CONCLUSIONS:

Cigarette smoke extract elicited a response important for regulation of angiogenesis and vascular permeability during inflammation, without evidence of DNA double-stand breaks associated with carcinogenesis. hVFFs are capable of participating in paracrine regulation of pathological blood vessel formation associated with cigarette smoking-related diseases (ie, Reinke edema). These cells express α7nAChR, an essential component of the cholinergic anti-inflammatory pathway regulated by the vagus nerve in certain tissues and a target of therapeutic agents.

KEYWORDS:

Vocal fold fibroblasts; cigarette smoke extract; vascular endothelial growth factor; γH2AX foci

PMID:
23494588
PMCID:
PMC4113205
DOI:
10.1002/lary.24052
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center