Cytokine gene expression and release from epithelial cells. A comparison study between healthy nasal mucosa and nasal polyps.
BACKGROUND
Epithelial cells release cytokines and they probably contribute to chronic inflammation detected in bronchial asthma, rhinitis and nasal polyposis.


OBJECTIVE
To investigate the effect of cultures on cytokine gene expression to compare epithelial cell cytokine release by both healthy nasal nucosa (HNM) and nasal polyps (NP), and the modulation by dexamethasone and to investigate which cytokines may promote eosinophil survival.


METHODS
Epithelials cells were cultured to confluence, human epithelial cell conditioned media generated with or without dexamethasone, and supernatants measured by ELISA. Cytokine gene expression was investigated by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
Fresh epithelial cells only expressed mRNA for intesleukin-8 (IL-8) and granulocyte macrophage-colony stimulating factor (GM-CSF) while cultured cells expressed mRNA for IL-1 beta, IL-6, IL-8, tumour necrosis factor-alpha (TNF alpha) and GM-CSF. Epithelial cells from NP significantly (P < 0.05) released more IL-8 (25431 +/- 3163 pg/mL), and GM-CSF (1229 +/- 391 pg/mL) than those from HNM (18604 +/- 1723 pg/mL for IL-8; and 611 +/- 98 pg/mL for GM-CSF). Dexamethasone 10 microM inhibited the release of all cytokines, this effect being similar (40-50%) in both HNM and NP, except for IL-6 which was higher in HNM. Eosinophil survival induced by epithelial cell secretions from both HNM and NP was strongly blocked by GM-CSF antibody while it was partially blocked by antibodies to TNF alpha and IL-8.


CONCLUSIONS
These findings suggest that although epithelial cell culture procedures may upregulate cytokine gene expression, nasal polyps may represent a more active inflammatory tissue by releasing more cytokines than healthy nasal mucosa this release being inhibited by steroids; and that, in addition to GM-CSF, other cytokines such as TNF alpha and IL-8, may also be involved in the promotion of eosinophil survival.
Unitat Mixta del FIS, Servei de Pneumologia i Allèrgia Respiratòria, Universitat de Barcelona, Catalonia, Spain.
J
J
Mullol
A
A
Xaubet
A
A
Gaya
J
J
Roca-Ferrer
E
E
López
J C
JC
Fernàndez
M D
MD
Fernàndez
C
C
Picado
D001483:Base Sequence; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000378:metabolism*; D009298:Nasal Polyps / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction
D016207:Cytokines; D007106:Immune Sera