Expression and regulation of osteopontin in chronic rhinosinusitis with nasal polyps.
BACKGROUND
Osteopontin (OPN) has been proposed to be associated with airway inflammation including asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). This study sought to evaluate the expression and regulation of the OPN in CRSwNP patients.


METHODS
Nasal polyp (NP) tissues and normal tissues were collected from 30 CRSwNP patients and 16 control subjects. The expression and regulation of OPN, as well eosinophil (EOS) accumulation and activation, were examined in nasal tissues using DNA microarray, immunohistochemical (IHC), immunofluorescent (IF) staining and qPCR analysis. Moreover, the regulation of OPN in nasal epithelial cells and its effects on migration and activation of EOS were evaluated in vitro using flow cytometry, ELISA, qPCR and Western blot, etc.


RESULTS
DNA microarray analysis identified OPN as one of the 19 upregulated genes in polyp tissues. The mean number of OPN(+) cells in polyp tissues was found to be significantly increased compared with the normal controls (P < 0.01), and OPN(+) cells in polyp tissues significantly correlated with tissue eosinophilia [major basic protein (MBP)(+) cells; r = 0.51, P < 0.01]. Accordingly, the mRNA and protein levels of OPN in NP tissues were significantly higher than those in normal controls (P < 0.01). Poly I:C, flagellin and TLR-9 agonist CpG ODN, as well as TNF-α, IFN-γ, IL-6, IL-17A and TGF-β, significantly increased OPN mRNA expression in cultured PECs and NECs (P < 0.05). Recombinant human OPN significantly promoted the migration of EOS, as well as enhanced EOS cationic protein (ECP) production, in an in vitro dispersed NP cells (DNPCs) culture system (P < 0.05).


CONCLUSIONS
OPN promotes eosinophilic nasal inflammation in CRSwNP patients, which may represent a promising therapeutic target.
Allergy and Cancer Center, Otorhinolarygology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Department of Otolaryngology, Guangzhou Women and Children's Medical Center, Guangzhou, China.
W-L
WL
Liu
H
H
Zhang
Y
Y
Zheng
H-T
HT
Wang
F-H
FH
Chen
L
L
Xu
Y
Y
Wei
Y-Q
YQ
Sun
J-B
JB
Shi
H-B
HB
Li
D000328:Adult; D016022:Case-Control Studies; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D016000:Cluster Analysis; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000235:genetics* / Q000276:immunology; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012220:Rhinitis / Q000235:genetics* / Q000276:immunology; D012852:Sinusitis / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D011994:Recombinant Proteins; D053495:Osteopontin
chronic rhinosinusitis; cytokine; eosinophil; epithelial cell; nasal polyps; osteopontin