Skip to main content

Tumor necrosis factor-alpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro.

Publication ,  Journal Article
Fischer, BM; Rochelle, LG; Voynow, JA; Akley, NJ; Adler, KB
Published in: American journal of respiratory cell and molecular biology
March 1999

Tumor necrosis factor (TNF)-alpha, a pluripotent cytokine implicated in the pathogenesis of airway inflammation, has been shown to provoke hypersecretion of mucin by airway epithelial cells in vitro. In this study, we investigated potential signaling pathways mediating TNF-alpha-induced mucin secretion using guinea pig tracheal epithelial (GPTE) cells in air-liquid interface culture. Exogenously applied TNF-alpha (human recombinant) stimulated mucin secretion in a concentration-dependent manner, with maximal effects at 10 to 15 ng/ml (286 to 429 U/ml). The pathway of stimulated secretion appeared to involve generation of intracellular nitric oxide (NO), activation of soluble guanylate cyclase (GC-S), production of cyclic guanosine monophosphate (cGMP), and activation of cGMP-dependent protein kinase (PKG). TNF-alpha increased production of nitrite and nitrate by GPTE cells; both mucin secretion and cGMP production were attenuated by NG-monomethyl-L-arginine (1 mM), a competitive inhibitor of nitric oxide synthase (NOS), or by the GC-S inhibitor LY83583 (50 microM); and mucin secretion in response to TNF-alpha or to the cGMP analogue dibutyryl cGMP (100 and 500 microM) was attenuated by the specific PKG inhibitor KT5823 (1 microM). Increased mucin secretion and increased cGMP production in response to TNF-alpha both appeared to be mediated by a phospholipase C that hydrolyzes phosphatidylcholine (PC-PLC), and by protein kinase C (PKC), since both responses were attenuated by either D609 (10 and 20 microg/ml), a specific PC-PLC inhibitor, or by each of three PKC inhibitors: Calphostin C (0.3 and 0.5 microM), bisindoylmaleimide (GF 109203X, Go 6850; 20 nM), or Ro31-8220 (10 microM). Collectively, the results suggest that TNF-alpha stimulates secretion of mucin by GPTE cells via a mechanism(s) dependent on PC-PLC and PKC, and involving activation of NOS, generation of NO, production of cGMP, and activation of PKG.

Altmetric Attention Stats
Dimensions Citation Stats

Published In

American journal of respiratory cell and molecular biology

DOI

EISSN

1535-4989

ISSN

1044-1549

Publication Date

March 1999

Volume

20

Issue

3

Start / End Page

413 / 422

Related Subject Headings

  • Type C Phospholipases
  • Tumor Necrosis Factor-alpha
  • Trachea
  • Signal Transduction
  • Respiratory System
  • Protein Kinases
  • Protein Kinase C
  • Nitric Oxide Synthase
  • Nitric Oxide
  • Mucins
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Fischer, B. M., Rochelle, L. G., Voynow, J. A., Akley, N. J., & Adler, K. B. (1999). Tumor necrosis factor-alpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro. American Journal of Respiratory Cell and Molecular Biology, 20(3), 413–422. https://doi.org/10.1165/ajrcmb.20.3.3393
Fischer, B. M., L. G. Rochelle, J. A. Voynow, N. J. Akley, and K. B. Adler. “Tumor necrosis factor-alpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro.American Journal of Respiratory Cell and Molecular Biology 20, no. 3 (March 1999): 413–22. https://doi.org/10.1165/ajrcmb.20.3.3393.
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. American journal of respiratory cell and molecular biology. 1999 Mar;20(3):413–22.
Fischer, B. M., et al. “Tumor necrosis factor-alpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro.American Journal of Respiratory Cell and Molecular Biology, vol. 20, no. 3, Mar. 1999, pp. 413–22. Epmc, doi:10.1165/ajrcmb.20.3.3393.
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. American journal of respiratory cell and molecular biology. 1999 Mar;20(3):413–422.

Published In

American journal of respiratory cell and molecular biology

DOI

EISSN

1535-4989

ISSN

1044-1549

Publication Date

March 1999

Volume

20

Issue

3

Start / End Page

413 / 422

Related Subject Headings

  • Type C Phospholipases
  • Tumor Necrosis Factor-alpha
  • Trachea
  • Signal Transduction
  • Respiratory System
  • Protein Kinases
  • Protein Kinase C
  • Nitric Oxide Synthase
  • Nitric Oxide
  • Mucins