Prolactin induces chitotriosidase expression in human macrophages through PTK, PI3-K, and MAPK pathways.
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.
Department of Biomedical Sciences, University of Catania, Catania, Italy.
Michelino
M
Di Rosa
Anna Maria
AM
Zambito
Anna Rita
AR
Marsullo
Giovanni
G
Li Volti
Lucia
L
Malaguarnera
D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006596:Hexosaminidases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology*; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011388:Prolactin / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
C412373:AG 1879; D000098:Acetophenones; D001578:Benzopyrans; D002070:Butadienes; D002867:Chromones; D007093:Imidazoles; D009025:Morpholines; D009570:Nitriles; D011725:Pyridines; D011743:Pyrimidines; D012333:RNA, Messenger; D020032:Tyrphostins; C113580:U 0126; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011388:Prolactin; D019833:Genistein; C085746:rottlerin; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D006596:Hexosaminidases; C086400:chitotriosidase; C093642:SB 203580