Effects of Proinflammatory Cytokines and Natural Products on Mucin Release from Cultured Hamster Tracheal Surface Epithelial Cells

  • Park, Ji-Sun (Department of Pharmacology, College of Medicine, Chungnom National University) ;
  • Kim, Hyoung-Soo (Department of Pharmacology, College of Medicine, Chungnom National University) ;
  • Seok, Jeong-Ho (Department of Pharmacology, College of Medicine, Chungnom National University) ;
  • Hur, Gang-Min (Department of Pharmacology, College of Medicine, Chungnom National University) ;
  • Park, Jong-Sun (Department of Pharmacology, College of Medicine, Chungnom National University) ;
  • Seo, Un-Kyo (Department of Oriental Medicine, College of Oriental Medicine, Dongguk University) ;
  • Lee, Choong-Jae (Department of Pharmacology, College of Medicine, Chungnom National University)
  • Published : 2004.12.21

Abstract

In this study, we investigated whether TNF-alpha, IL-1beta, CTMA (carboxymethyl trimethylammonium) and LPD (Lup-20[29]-ene-3beta,28-diol) affect mucin release from airway goblet cells and compared the activities of these agents with the inhibitory action of PLL and the stimulatory action of ATP on mucin release. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled with $^3H-glucosamine$ for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on $^3H-mucin$ release. The results were as follows: TNF-alpha, CTMA and LPD increased mucin release at the highest concentration, but IL-1beta did not. We conclude that CTMA and LPD can stimulate mucin release by directly acting on airway mucin-secreting cells, and suggest that these agents should be further investigated for the possible use as mild expectorants during the treatment of chronic airway diseases.

Keywords

References

  1. Bernard P, Scior T, Didier B, Hibert M, Berthon JY. Ethnopharmacology and bioinformatic combination for leads discovery: application to phospholipase A2 inhibitors. Phytochemistry 58: 865-874, 2003
  2. Chiang LC, Ng LT, Chiang W, Chang MY, Lin CC. Immunomodulatory activities of flavonoids, monoterpenoids, triterpenoids, iridoid glycosides and phenolic compounds of Plantago species. Planta Med 69: 600-604, 2003 https://doi.org/10.1055/s-2003-41113
  3. Ellis EF. Asthma in childhood. J Allergy Clin Immunol 72(suppl): 526-539, 1985
  4. Fischer BM, Rochelle LG, Voynow JA, Akley NJ, Adler KB. TNFalpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro. Am J Respir Cell Mol Biol 20: 413-422, 1999 https://doi.org/10.1165/ajrcmb.20.3.3393
  5. Ismali H, Sosa S, Brkic D, Fkih-Tetouani S, llidrissi A, Touati D, Aqin RP et al. Topical anti-inflammatory activity of extracts and compounds from Thymus broussonettii. J Pharm Pharmacol 54: 1137-1140, 2002 https://doi.org/10.1211/002235702320266316
  6. Kim KC, McCracken K, Lee BC, Shin CY, Jo MJ, Lee CJ, Ko KH. Airway goblet cell mucin: its structure and regulation of secretion. Eur Respir J 10: 2644-2649, 1997 https://doi.org/10.1183/09031936.97.10112644
  7. Kim KC, Wasano K, Niles RM, Schuster JE, Stone PJ, Brody JS. Human neutrophil elastase releases cell surface mucins from primary cultures of hamster tracheal epithelial cells. Proc Natl Acad Sci USA 84: 9304-9308, 1987 https://doi.org/10.1073/pnas.84.24.9304
  8. Kim Y, Kwon E, Park D, Song S, Yoon S, Baek S. IL-1beta induces MUC2 and MUC5AC synthesis through cyclooxygenase-2 in NCI-H292 cells. Mol Pharmacol 62: 1112-1118, 2002 https://doi.org/10.1124/mol.62.5.1112
  9. Ko KH, Lee CJ, Shin CY, Jo M, Kim KC. Inhibition of mucin release from airway goblet cells by polycationic peptides. Am J Physiol 277: L811-L815, 1999
  10. Manez S, Recio MC, Giner RM, Rios JL. Effect of selected triterpenoids on chronic dermal inflammation. Eur J Pharmacol 334: 103-105, 1997 https://doi.org/10.1016/S0014-2999(97)01187-4
  11. Mutschler E, Derendorf H. Drug actions. Boca Raton, CRC press, Florida., p 410-411, 1995
  12. Newhouse MT, Biennenstock J. Respiratory tract defense mechanism. In: Baum GL, Wolinsky E ed, Textbook of pulmonary disease. 3rd ed. Little Brown and Company, Boston, Massachusetts, 1983
  13. Recio MC, Giner RM, Manez S, Gueho J, Julien HR, Hostettmann K, Rios JL. Investigations on the steroidal anti-inflammatory activity of triterpenoids from Diospyros leucomelas. Planta Med 61: 9-12, 1995. https://doi.org/10.1055/s-2006-957988
  14. Research institute of natural products in Seoul National University, Treatise on asian herbal medicines. Haksul-pyunsu-kwan, Seoul, p 4517, 2003
  15. Shao MX, Ueki IF, Nadel JA. TNF-alpha converting enzyme mediated MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci USA 100(20):11618-11623, 2003 https://doi.org/10.1073/pnas.1534804100
  16. Song KS, Lee WJ, Chung KC, Koo JS, Yang EJ, Choi JY, Yoon JH. IL-1beta and TNF-alpha induced MUC5AC overexpression through a mechanism involving ERK/p38 mitogen-activated protein kinase-MSK1-CREB activation in human airway epithelial cells. J Biol Chem 278(26): 23243-23250, 2003 https://doi.org/10.1074/jbc.M300096200
  17. Stromaier W, Redl H, Schlag G. Studies on the potential role of a semisynthetic surfactant preparation in an experimental aspiration trauma in rabbits. Exp Lung Res 16(2): 101-110, 1990 https://doi.org/10.3109/01902149009087875
  18. Stromaier W, Schlag G. Experimental aspiration trauma: comparison of steroid treatment versus exogenous natural surfactant. Exp Lung Res 19(3): 397-405, 1993 https://doi.org/10.3109/01902149309064354
  19. Wasano K, Kim KC, Niles RM, Brody JS. Membrane differentiation markers of airway epithelial secretory cells. J Histochem Cytochem 36: 167-17, 1988 https://doi.org/10.1177/36.2.3335774
  20. Yamashita K, Lu H, Lu J, Chen G, Yokoyama T, Sagara Y, Manabe M et al. Effect of three triterpenoids lupeol, betulin and betulinic acid on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils. Clinica Chimica Acta 325: 91-96, 2002 https://doi.org/10.1016/S0009-8981(02)00252-8