Tuberc Respir Dis.  2011 Mar;70(3):218-223. 10.4046/trd.2011.70.3.218.

Effects of Curcumin and Genistein on Phorbol Ester or Tumor Necrosis Factor-alpha-Induced Mucin Production from Human Airway Epithelial Cells

Affiliations
  • 1Department of Pharmacology, Chungnam National University College of Medicine, Daejeon, Korea. LCJ123@cnu.ac.kr
  • 2LG Life Science, Seoul, Korea.
  • 3Department of Radiologic Technology, Daegu Health College, Daegu, Korea.
  • 4Pulmonology Section, Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea.

Abstract

BACKGROUND
We investigated whether curcumin and genistein affect the MUC5AC mucin production from human airway epithelial cells that is induced by phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-alpha (TNF-alpha).
METHODS
Confluent NCI-H292 cells were pretreated with each agent for 30 min and then stimulated with PMA or TNF-alpha for 24 hours. MUC5AC mucin production was measured by an ELISA.
RESULTS
(1) Curcumin dose-dependently inhibited the production of MUC5AC mucin that was induced by PMA or TNF-alpha; (2) Genistein inhibited PMA-induced MUC5AC mucin production. However, it did not decrease TNF-alpha-induced MUC5AC mucin production.
CONCLUSION
These results suggest that curcumin and genistein inhibit the production of airway mucin induced by PMA.

Keyword

Mucin 5AC; Curcumin; Genistein

MeSH Terms

Curcumin
Epithelial Cells
Genistein
Humans
Mucin 5AC
Mucins
Necrosis
Phorbols
Tumor Necrosis Factor-alpha
Curcumin
Genistein
Mucin 5AC
Mucins
Phorbols
Tumor Necrosis Factor-alpha

Figure

  • Figure 1 Effect of curcumin on PMA-induced MUC5AC mucin production from NCI-H292 cells. NCI-H292 cells were pretreated with varying concentrations of curcumin for 30 min and then stimulated with PMA (10 ng/mL) for 24 hours. Cell lysates were collected for measurement of MUC5AC mucin production by ELISA. Means of individual group were converted to percent control and expressed as mean±SEM. The difference between groups was assessed using one-way ANOVA and Student's t-test for unpaired samples. p<0.05 was considered as significantly different. Each bar represents a mean±SEM. of 3~4 culture wells in comparison with that of a control set at 100%. *Significantly different from control (p<0.05), †Significantly different from PMA alone (p<0.05). SEM: standard error of the mean; cont: control; C: curcumin, concentration unit is µM.; PMA: phorbol 12-myristate 13-acetate.

  • Figure 2 Effect of curcumin on TNF-α-induced MUC5AC mucin production from NCI-H292 cells. NCI-H292 cells were pretreated with various concentrations of curcumin for 30min and then stimulated with TNF-α (0.2 nM) for 24 hours. Cell lysates were collected for measurement of MUC5AC mucin production by ELISA. Means of individual group were converted to percent control and expressed as mean±SEM. The difference between groups was assessed using one-way ANOVA and Student's t-test for unpaired samples. p<0.05 was considered as significantly different. Each bar represents a mean±SEM. of 3~4 culture wells in comparison with that of control set at 100%. *Significantly different from control (p<0.05), †Significantly different from TNF-α alone (p<0.05). SEM: standard error of the mean; cont: control; C: curcumin, concentration unit is µM.; PMA: phorbol 12-myristate 13-acetate; TNF: tumor necrosis factor.

  • Figure 3 Effect of genistein on PMA-induced MUC5AC mucin production from NCI-H292 cells. NCI-H292 cells were pretreated with varying concentrations of genistein for 30 min and then stimulated with PMA (10 ng/mL) for 24 hours. Cell lysates were collected for measurement of MUC5AC mucin production by ELISA. Means of individual group were converted to percent control and expressed as mean±SEM. The difference between groups was assessed using one-way ANOVA and Student's t-test for unpaired samples. p<0.05 was considered as significantly different. Each bar represents a mean±SEM of 3~4 culture wells in comparison with that of a control set at 100%. *Significantly different from control (p<0.05), †Significantly different from PMA alone (p<0.05). SEM: standard error of the mean; cont: control; PMA: phorbol 12-myristate 13-acetate; G: genistein, concentration unit is µM.

  • Figure 4 Effect of genistein on TNF-α-induced MUC5AC mucin production from NCI-H292 cells. NCI-H292 cells were pretreated with various concentrations of genistein for 30 min and then stimulated with TNF-α (0.2 nM) for 24 hours. Cell lysates were collected for measurement of MUC5AC mucin production by ELISA. Means of individual group were converted to percent control and expressed as mean±SEM. The difference between groups was assessed using one-way ANOVA and Student's t-test for unpaired samples. p<0.05 was considered as significantly different. Each bar represents a mean±SEM. of 3~4 culture wells in comparison with that of control set at 100%. *Significantly different from control (p<0.05). ELISA: enzyme-linked immunosorbent assay; cont: control; G: genistein, concentration unit is µM.


Reference

1. Voynow JA, Rubin BK. Mucins, mucus, and sputum. Chest. 2009. 135:505–512.
2. Yuan-Chen Wu D, Wu R, Reddy SP, Lee YC, Chang MM. Distinctive epidermal growth factor receptor/extracellular regulated kinase-independent and -dependent signaling pathways in the induction of airway mucin 5B and mucin 5AC expression by phorbol 12-myristate 13-acetate. Am J Pathol. 2007. 170:20–32.
3. Rogers DF, Barnes PJ. Treatment of airway mucus hypersecretion. Ann Med. 2006. 38:116–125.
4. Lee CJ, Lee JH, Seok JH, Hur GM, Park Js J, Bae S, et al. Effects of betaine, coumarin and flavonoids on mucin release from cultured hamster tracheal surface epithelial cells. Phytother Res. 2004. 18:301–305.
5. Lee CJ, Lee JH, Seok JH, Hur GM, Park YC, Seol IC, et al. Effects of baicalein, berberine, curcumin and hesperidin on mucin release from airway goblet cells. Planta Med. 2003. 69:523–526.
6. Lee CJ, Seok JH, Hur GM, Lee JH, Park JS, Seol IC, et al. Effects of ursolic acid, betulin and sulfur-containing compounds on mucin release from airway goblet cells. Planta Med. 2004. 70:1119–1122.
7. Chang IM. Treatise on Asian herbal medicines. 2003. 1st ed. Seoul: Hak Sool Pyun Soo Gwan.
8. Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol. 2006. 71:1397–1421.
9. Dohrman A, Miyata S, Gallup M, Li JD, Chapelin C, Coste A, et al. Mucin gene (MUC 2 and MUC 5AC) upregulation by Gram-positive and Gram-negative bacteria. Biochim Biophys Acta. 1998. 1406:251–259.
10. Li JD, Dohrman AF, Gallup M, Miyata S, Gum JR, Kim YS, et al. Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proc Natl Acad Sci USA. 1997. 94:967–972.
11. Ram A, Das M, Ghosh B. Curcumin attenuates allergen-induced airway hyperresponsiveness in sensitized guinea pigs. Biol Pharm Bull. 2003. 26:1021–1024.
12. Moon DO, Kim MO, Lee HJ, Choi YH, Park YM, Heo MS, et al. Curcumin attenuates ovalbumin-induced airway inflammation by regulating nitric oxide. Biochem Biophys Res Commun. 2008. 375:275–279.
13. Berger AL, Randak CO, Ostedgaard LS, Karp PH, Vermeer DW, Welsh MJ. Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl-channel activity. J Biol Chem. 2005. 280:5221–5226.
14. Andersson C, Servetnyk Z, Roomans GM. Activation of CFTR by genistein in human airway epithelial cell lines. Biochem Biophys Res Commun. 2003. 308:518–522.
15. Kalhan R, Smith LJ, Nlend MC, Nair A, Hixon JL, Sporn PH. A mechanism of benefit of soy genistein in asthma: inhibition of eosinophil p38-dependent leukotriene synthesis. Clin Exp Allergy. 2008. 38:103–112.
16. Assem ES, Wan BY, Peh KH, Pearce FL. Effect of genistein on agonist-induced airway smooth muscle contraction. Inflamm Res. 2006. 55:Suppl 1. S13–S14.
17. Duan W, Kuo IC, Selvarajan S, Chua KY, Bay BH, Wong WS. Antiinflammatory effects of genistein, a tyrosine kinase inhibitor, on a guinea pig model of asthma. Am J Respir Crit Care Med. 2003. 167:185–192.
18. Heo HJ, Lee SY, Lee MN, Lee HJ, Seok JH, Lee CJ. Genistein and curcumin suppress epidermal growth factor-induced MUC5AC mucin production and gene expression from human airway epithelial cells. Phytother Res. 2009. 23:1458–1461.
19. Fischer BM, Rochelle LG, Voynow JA, Akley NJ, Adler KB. Tumor necrosis factor-alpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro. Am J Respir Cell Mol Biol. 1999. 20:413–422.
20. Shao MX, Ueki IF, Nadel JA. Tumor necrosis factor alpha-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci USA. 2003. 100:11618–11623.
21. Song KS, Lee WJ, Chung KC, Koo JS, Yang EJ, Choi JY, et al. Interleukin-1 beta and tumor necrosis factor-alpha induce MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinases-MSK1-CREB activation in human airway epithelial cells. J Biol Chem. 2003. 278:23243–23250.
22. Chung KF. Cytokines in chronic obstructive pulmonary disease. Eur Respir J Suppl. 2001. 34:50s–59s.
23. Cohn L, Whittaker L, Niu N, Homer RJ. Cytokine regulation of mucus production in a model of allergic asthma. Novartis Found Symp. 2002. 248:201–213.
24. Hewson CA, Edbrooke MR, Johnston SL. PMA induces the MUC5AC respiratory mucin in human bronchial epithelial cells, via PKC, EGF/TGF-alpha, Ras/Raf, MEK, ERK and Sp1-dependent mechanisms. J Mol Biol. 2004. 344:683–695.
25. Park SJ, Kang SY, Kim NS, Kim HM. Phosphatidylinositol 3-kinase regulates PMA-induced differentiation and superoxide production in HL-60 cells. Immunopharmacol Immunotoxicol. 2002. 24:211–226.
26. Takeyama K, Dabbagh K, Lee HM, Agustí C, Lausier JA, Ueki IF, et al. Epidermal growth factor system regulates mucin production in airways. Proc Natl Acad Sci USA. 1999. 96:3081–3086.
Full Text Links
  • TRD
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr