Clin Exp Otorhinolaryngol.  2014 Jun;7(2):112-118.

Dexamethasone Induces Apoptosis of Nasal Polyp-Derived Tissue Cultures Through JNK and p38 MAPK Activation

• Lee TH
• Nam JG
• Lee HM
• Kim BY
• Kang MK
• Bae WY
• Hur DY
• Park SK

Abstract

OBJECTIVES
Glucocorticoids, such as dexamethasone (DEX), increase apoptosis in a variety of white cells in nasal polyps and apoptosis is an important factor in the resolution of inflammation. However, the mechanism of glucocorticoids induced apoptosis in nasal polyp remains unclear. In this study the authors evaluated which pathways were engaged in apoptosis induced by DEX in an ex vivo model of nasal polyps.
METHODS
Nasal polyp tissues were cultured using an air-liquid interface method. Cultures were maintained in the absence or presence of DEX (10 or 100 microM) for 24 hours. To investigate the involvement of the apoptotic signaling pathways in nasal polyp, such as caspase cascades, Fas-FasL signaling pathway, mitochondrial pathway and p38 mitogen-activated protein kinase (MAPK)/JNK pathway, the authors performed reverse transcription-polymerase chain reaction and Western blotting.
RESULTS
The expression ratios of FasL, activated form of caspase-8, caspase-9, and caspase-3 were significantly higher in DEX-treated polyps (P<0.01). In the Bcl-2 family expression, the anti-apoptotic molecules, Bcl-2 and Bcl-XL decreased, but pro-apoptotic molecules, Bax increased, and Bid and Bad were activated. In the conventional MAPKs, JNK, and the phospho-p38 MAPK were significantly higher, but phospho-extracellular signal-regulated kinase (ERK)1/2 was significantly lower in DEX-treated polyps (P<0.01).
CONCLUSION
DEX induces apoptosis of nasal polyp via caspase cascades, Fas-FasL signaling pathway, mitochondrial pathway and p38 MAPK/JNK pathway.

Keyword

Apoptosis; Glucocorticoids; Nasal polyps; Organ culture; Ex vivo; MAPKs

MeSH Terms

Apoptosis*
Blotting, Western
Caspase 3
Caspase 8
Caspase 9
Dexamethasone*
Glucocorticoids
Humans
Inflammation
Nasal Polyps
Organ Culture Techniques
p38 Mitogen-Activated Protein Kinases*
Phosphotransferases
Polyps
Protein Kinases
Caspase 3
Caspase 8
Caspase 9
Dexamethasone
Glucocorticoids
Phosphotransferases
Protein Kinases
p38 Mitogen-Activated Protein Kinases

Figure

• 

  Fig. 1 Reverse transcription-polymerase chain reaction analysis for mRNA of FasL and Bcl-2 family molecules. The bars indicate the mean±SD. DEX, dexamethasone. *P<0.01.

• 

  Fig. 2 Western blot analysis for FasL, Bcl-2, Bcl-XL, Bax, Bad, p-Bad, Bid, and tBid. The bars indicate the mean±SD. DEX, dexamethasone. *P<0.01.

• 

  Fig. 3 Western blot analysis for caspases and poly(ADP-ribose) polymerase (PARP). The bars indicate the mean±SD. DEX, dexamethasone. *P<0.01. †P<0.05.

• 

  Fig. 4 Western blot analysis for Akt, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase. The bars indicate the mean±SD. *P<0.01.

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