Skip to main content

p38 Mitogen-activated protein kinase modulates exocrine secretion in rabbit lacrimal gland

Abstract

The lacrimal gland (LG) is an exocrine gland important for secretion of the tear film. The kinase p38 has important signal transduction functions, e.g. in gene transcription, but has previously not been known to modulate exocrine secretion. The aim of the current study was to investigate the role of p38 in carbachol (Cch)-induced LG secretion in LG acinar cells in vitro. Western blotting was used to determine the phosphorylation status of p38 and p42/44 and determine expression of p38 isoforms. To determine the effect of p38 inhibition on LG secretion, PD 169316, a general p38 inhibitor, and SB 239063, an inhibitor of p38α and β, were added to the cells prior to secretion measurements. The results revealed activation of p38 mediated by Cch stimulation and inhibition of Cch-induced secretion as a result of p38 inhibition. The inhibition was observed with PD 169316 isoforms, but not with SB 239063. The p38δ isoform was shown to have robust expression both by Western blotting of acinar cells and immunofluorescence of the whole gland. In conclusion, p38 activation mediates secretion in cholinergic stimulation of rabbit LG cells.

Abbreviations

Cch:

carbachol

JNK:

c-jun N-terminal kinase

DAG:

diacylglycerol

IP3 :

inositol triphosphate

LG:

lacrimal gland

MAPK:

mitogen-activated protein kinase

PBS:

phosphate buffered saline

References

  1. 1.

    Raingeaud, J., Gupta, S., Rogers, J.S., Dickens, M., Han, J., Ulevitch, R.J. and Davis, R.J. Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J. Biol. Chem. 270 (1995) 7420–7426.

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Cuadrado, A. and Nebreda, A.R. Mechanisms and functions of p38 MAPK signalling. Biochem. J. 429 (2010) 403–417.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Dartt, D.A. Neural regulation of lacrimal gland secretory processes: relevance in dry eye diseases. Prog. Retin. Eye Res. 28 (2009) 155–177.

    PubMed  Article  Google Scholar 

  4. 4.

    Godfrey, P.P. and Putney, J.W., Jr. Receptor-mediated metabolism of the phosphoinositides and phosphatidic acid in rat lacrimal acinar cells. Biochem. J. 218 (1984) 187–195.

    PubMed  CAS  Google Scholar 

  5. 5.

    Funaki, C., Hodges, R.R. and Dartt, D.A. Role of cAMP inhibition of p44/p42 mitogen-activated protein kinase in potentiation of protein secretion in rat lacrimal gland. Am. J. Physiol. Cell Physiol. 293 (2007) C1551–1560.

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Andersson, S.V., Edman, M.C., Bekmezian, A., Holmberg, J., Mircheff, A.K. and Gierow, J.P. Characterization of beta-hexosaminidase secretion in rabbit lacrimal gland. Exp. Eye Res. 83 (2006) 1081–1088.

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Takeichi, T., Sugiura, K., Muro, Y., Matsumoto, K., Ogawa, Y., Futamura, K., Kaminuma, O., Hashimoto, N., Shimoyama, Y., Saito, H. and Tomita, Y. Overexpression of LEDGF/DFS70 induces IL-6 via p38 activation in HaCaT cells, similar to that seen in the psoriatic condition. J. Invest. Dermatol. 130 (2010) 2760–2767.

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Koon, H.K., Chan, P.S., Wu, Z.G., Wong, R.N., Lung, M.L., Chang, C.K. and Mak, N.K. Role of mitogen-activated protein kinase in Zn-BC-AM PDT-induced apoptosis in nasopharyngeal carcinoma cells. Cell. Biochem. Funct. 28 (2010) 239–248.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Andersson, S.V., Sjogren, E.C., Magnusson, C. and Gierow, J.P. Sequencing, expression, and enzymatic characterization of betahexosaminidase in rabbit lacrimal gland and primary cultured acinar cells. Glycobiology 15 (2005) 211–220.

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Carlsson, S.K., Edman, M.C., Delbro, D. and Gierow, J.P. Adenosine A2 receptor presence and synergy with cholinergic stimulation in rabbit lacrimal gland. Curr. Eye Res. 35 (2010) 466–474.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Fujita-Yoshigaki, J., Qi, B., Narita, T. and Sugiya, H. Parotid acinar cells transiently change to duct-like cells during epithelial-mesenchymal transition. J. Med. Invest. 56Suppl (2009) 258–259.

    PubMed  Article  Google Scholar 

  12. 12.

    Wu, D.M., Zhao, D., Li, D.Z., Xu, D.Y., Chu, W.F. and Wang, X.F. Maslinic acid induces apoptosis in salivary gland adenoid cystic carcinoma cells by Ca2+-evoked p38 signaling pathway. Naunyn Schmiedebergs Arch. Pharmacol. 383 (2011) 321–330.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Williard, D.E., Twait, E., Yuan, Z., Carter, A.B. and Samuel, I. Nuclear factor kappa B-dependent gene transcription in cholecystokinin- and tumor necrosis factor-alpha-stimulated isolated acinar cells is regulated by p38 mitogen-activated protein kinase. Am. J. Surg. 200 (2010) 283–290.

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Zoukhri, D., Macari, E., Choi, S.H. and Kublin, C.L. c-Jun NH2-terminal kinase mediates interleukin-1beta-induced inhibition of lacrimal gland secretion. J. Neurochem. 96 (2006) 126–135.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Funaki, C., Hodges, R.R. and Dartt, D.A. Identification of the Raf-1 signaling pathway used by cAMP to inhibit p42/p44 MAPK in rat lacrimal gland acini: role in potentiation of protein secretion. Invest. Ophthalmol. Vis. Sci. 51 (2010) 6321–6328.

    PubMed  Article  Google Scholar 

  16. 16.

    Morimoto-Tochigi, A., Walkup, R.D., Nakajima, E., Shearer, T.R. and Azuma, M. Mechanism for carbachol-induced secretion of lacritin in cultured monkey lacrimal acinar cells. Invest. Ophthalmol. Vis. Sci. 51 (2010) 4395–4406.

    PubMed  Article  Google Scholar 

  17. 17.

    Ota, I., Zoukhri, D., Hodges, R.R., Rios, J.D., Tepavcevic, V., Raddassi, I., Chen, L.L. and Dartt, D.A. Alpha 1-adrenergic and cholinergic agonists activate MAPK by separate mechanisms to inhibit secretion in lacrimal gland. Am. J. Physiol. Cell Physiol. 284 (2003) C168–178.

    PubMed  CAS  Google Scholar 

  18. 18.

    Wang, X.S., Diener, K., Manthey, C.L., Wang, S., Rosenzweig, B., Bray, J., Delaney, J., Cole, C.N., Chan-Hui, P.Y., Mantlo, N., Lichenstein, H.S., Zukowski, M. and Yao, Z. Molecular cloning and characterization of a novel p38 mitogen-activated protein kinase. J. Biol. Chem. 272 (1997) 23668–23674.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Stina K. Carlsson.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Carlsson, S.K., Gierow, J.P. p38 Mitogen-activated protein kinase modulates exocrine secretion in rabbit lacrimal gland. Cell Mol Biol Lett 17, 1–10 (2012). https://doi.org/10.2478/s11658-011-0031-y

Download citation

Key words

  • p38 mitogen-activated protein kinase
  • Lacrimal gland
  • Exocrine glands
  • Signal transduction
  • Cholinergic receptors