Zinc suppresses IL-6 synthesis by prostaglandin F2alpha in osteoblasts: inhibition of phospholipase C and phospholipase D

J Cell Biochem. 2002;85(3):621-8. doi: 10.1002/jcb.10166.


We previously reported that prostaglandin F2alpha (PGF2alpha) induces phosphoinositide hydrolysis by phospholipase C and phosphatidylcholine hydrolysis by phospholipase D through heterotrimeric GTP-binding protein, resulting in the activation of protein kinase C (PKC) in osteoblast-like MC3T3-E1 cells and that PGF2alpha stimulates the synthesis of interleukin-6 (IL-6) via PKC-dependent p44/p42 mitogen-activated protein (MAP) kinase activation. In the present study, we investigated whether zinc affects the PGF2alpha-induced IL-6 synthesis in these cells. Zinc complex of l-carnosine (l-CAZ) dose-dependently suppressed the PGF2alpha-stimulated IL-6 synthesis. In addition, zinc alone reduced the IL-6 synthesis. L-CAZ suppressed the PGF2alpha-induced p44/p42 MAP kinase phosphorylation. However, the p44/p42 MAP kinase phosphorylation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a direct activator of PKC, or NaF, a direct activator of GTP-binding protein, was not affected by l-CAZ. l-CAZ reduced the PGF2alpha-stimulated formation of inositol phosphates and choline. However, l-CAZ did not affect the formation of inositol phosphates or choline induced by NaF. These results strongly suggest that zinc reduces PGF2alpha-induced IL-6 synthesis via suppression of phosphoinositide-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D in osteoblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carnosine / analogs & derivatives
  • Carnosine / pharmacology
  • Cell Line
  • Choline / metabolism
  • Dinoprost / metabolism*
  • Dinoprost / pharmacology
  • Dose-Response Relationship, Drug
  • Inositol Phosphates / metabolism
  • Interleukin-6 / biosynthesis*
  • Mice
  • Mitogen-Activated Protein Kinase 1 / drug effects
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism*
  • Phospholipase D / antagonists & inhibitors
  • Phospholipase D / metabolism*
  • Phosphorylation
  • Sodium Fluoride / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Type C Phospholipases / antagonists & inhibitors
  • Type C Phospholipases / metabolism*
  • Zinc / chemistry
  • Zinc / pharmacology*
  • Zinc Sulfate / pharmacology


  • Inositol Phosphates
  • Interleukin-6
  • Zinc Sulfate
  • Carnosine
  • Sodium Fluoride
  • Dinoprost
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Type C Phospholipases
  • Phospholipase D
  • Zinc
  • Choline
  • Tetradecanoylphorbol Acetate