Eosinophil expression of transforming growth factor-beta and its receptors in nasal polyposis: role of the cytokines in this disease process.
OBJECTIVE
Nasal polyposis (NP) is characterized by an increase in inflammatory processes including fibrosis. Because transforming growth factor beta (TGF-beta) has been proven to induce fibrosis, we hypothesize that TGF-beta and its receptors are present in NP and influence polyp development.


METHODS
To test this hypothesis, we evaluated distribution (immunohistochemistry) of TGF-beta isoforms (TGF-beta 1, TGF-beta 2, and TGF-beta 3) and its receptors [(TGF-beta(RI) & TGF-beta(RII)] in NP from 36 NP patients and in five normal sinus tissue specimens obtained from septoplasty/inferior turbinectomy. Tissue levels of TGF-beta 1 and TGF-beta 2 levels were determined by enzyme-linked immunosorbent assay (ELISA) and protein content was determined by Bio Rad assay (Bio Rad, Richmond, CA). All tissue levels of TGF-beta were normalized and expressed as pg of TGF-beta per mg of total protein (pg/mg TP).


RESULTS
Immunohistochemical studies showed eosinophils as the major cells positively staining for TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-beta(RI), and TGF-beta. In fibrotic sections, increased staining of eosinophils, fibroblast, and mononuclear cells was found for all three isoforms and both receptors. Evaluation of tissue levels indicated mean levels of TGF-beta 1 in the NP were 11.64 +/- 22.12 pg/mg TP versus normal control mean 44.36 +/- 22.12 pg/mg TP.TGF-beta 2 mean levels were 11.46 +/- 23.73 pg/mg TP versus normal control mean of 2.03 +/- 1.13 pg/mg TP. NP showed decreased expression of TGF-beta 1 and enhanced expression of TGF-beta 2 isoforms with presence of their receptors. Higher levels of TGF-beta 2 correlated with an increase in previous polypectomies perhaps indicative of severity of disease (P < or = .0001).


CONCLUSIONS
Our studies show the presence of the TGF-beta isoforms and receptors in NP tissue. The results support our hypothesis that the eosinophil continues to be a pivotal inflammatory cell in NP, a differential regulation may govern the activity of TGF-beta in NP, and hence, the TGF-beta family of cytokines and receptors likely play a key role in controlling NP formation.
Eisma
R J
RJ
Department of Surgery, University of Connecticut Health Center, School of Medicine, Farmington 06030-3105, USA.
Allen
J S
JS
Lafreniere
D
D
Leonard
G
G
Kreutzer
D L
DL
D000328:Adult; D000368:Aged; D046508:Culture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009298:Nasal Polyps / Q000737:chemistry / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta