Prolactin induces chitotriosidase expression in human macrophages through PTK, PI3-K, and MAPK pathways

J Cell Biochem. 2009 Aug 1;107(5):881-9. doi: 10.1002/jcb.22186.

Abstract

We previously reported that prolactin (PRL) induces chitotriosidase (CHIT-1) mRNA expression in human macrophages. In this investigation we determined the signaling pathways involved in CHIT-1 induction in response to PRL. The CHIT-1 induction PRL-mediated was reduced by wortmannin and LY-294002, inhibitors of phosphatidylinositol 3-kinase (PI3-K) and by genistein an inhibitor of protein tyrosine kinase (PTK). Pre-treatment of macrophages with SB203580, a specific inhibitor of the mitogen-activated kinases (MAPK) p38, or with U0126, an inhibitor of MAPK p44/42, prevented both basal and exogenous PRL-mediated CHIT-1 expression. No significant effects on CHIT-1 induction PRL-mediated were observed with a protein kinase C inhibitor (PKC), rottlerin, or with an Src inhibitor, PP2, or with JAK2 inhibitor, AG490. In addition, PRL induced a phosphorylation of AKT that was prevented both by the two MAPK inhibitors SB203580 and U0126 and by the PI3-K inhibitors wortmannin and LY-294002. In conclusion, our results indicate that PRL up-regulated CHIT-1 expression via PTK, PI3-K, MAPK, and signaling transduction components.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / pharmacology
  • Benzopyrans / pharmacology
  • Butadienes / pharmacology
  • Chromones / pharmacology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Genistein / pharmacology
  • Hexosaminidases / genetics
  • Hexosaminidases / metabolism*
  • Humans
  • Imidazoles / pharmacology
  • MAP Kinase Signaling System / drug effects*
  • Macrophages / drug effects*
  • Macrophages / enzymology*
  • Monocytes / drug effects
  • Monocytes / enzymology
  • Morpholines / pharmacology
  • Nitriles / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation / drug effects
  • Prolactin / pharmacology*
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyridines / pharmacology
  • Pyrimidines / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tyrphostins / pharmacology

Substances

  • AG 1879
  • Acetophenones
  • Benzopyrans
  • Butadienes
  • Chromones
  • Imidazoles
  • Morpholines
  • Nitriles
  • Pyridines
  • Pyrimidines
  • RNA, Messenger
  • Tyrphostins
  • U 0126
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Prolactin
  • Genistein
  • rottlerin
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-akt
  • Hexosaminidases
  • chitotriosidase
  • SB 203580