Dual action of TGF-beta1 on nasal-polyp derived fibroblasts.
OBJECTIVE
Transforming growth factor beta-1 (TGF-beta1) is a known fibrogenic factor with immunosuppressive properties. We wanted to determine the effect of stimulation with TGF-beta1 on nasal polyp-derived fibroblasts and assess the role this molecule would have in polyp formation and growth.


METHODS
Nasal-polyp derived fibroblasts were cultured with or without TGF-beta1, and proliferation and cytokine secretion were measured.


METHODS
Fibroblasts were isolated from nasal polyps following endoscopic surgery. Cells were plated and grown until confluent, after which they were split and used in assays. Cells were stimulated with TGF- beta1 and mRNA collected after 16 hours, supernatants after 72 hours, and proliferation measured after 96 hours of culture.


RESULTS
TGF-beta1 significantly (P < .02) increased proliferation of nasal-polyp derived fibroblasts. We examined the expression of inflammatory cytokines and found that TGF-beta1 decreased expression of CCL2 (MCP-1), CCL5 (RANTES), CCL11 (eotaxin), granulocyte-colony stimulating factor (G-CSF), and GM-CSF (P < .05). In contrast, incubation with TGF-beta1 increased fibronectin, procollagen, vascular endothelial growth factor (VEGF), and TGF-beta2 protein production (P < .05). For select samples, we confirmed that the increased protein production was due to increased mRNA expression.


CONCLUSIONS
These studies suggest that TGF-beta1 expression in polyp tissue can have dual effects. One role is to act as an anti-inflammatory agent shown by the ability to inhibit pro-inflammatory mRNA and protein production. At the same time, TGF-beta1 expression leads to increases in factors involved in fibrosis and angiogenesis, promoting remodeling and cell growth.
Little
Stewart C
SC
Department of Otolaryngology-HNS, University of Virginia Health System, Charlottesville, VA 22908, USA. sl3fj@virginia.edu
Early
S Brandon
SB
Woodard
Charles R
CR
Shonka
David C
DC
Han
Joseph K
JK
Borish
Larry
L
Steinke
John W
JW
D049109:Cell Proliferation; D054413:Chemokine CCL11 / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism*; D005353:Fibronectins / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D009298:Nasal Polyps / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism*
C111835:CCL2 protein, human; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D017931:DNA Primers; D018076:DNA, Complementary; D005353:Fibronectins; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor