Role of protein kinase pathways in IL-1-induced chemoattractant expression by human mesangial cells

Kidney Int. 1994 Oct;46(4):1059-68. doi: 10.1038/ki.1994.367.


Human mesangial cells produce the monocyte-specific chemotactic factor monocyte chemoattractant protein-1 (MCP-1) in response to a variety of stimuli, including the pro-inflammatory cytokine interleukin-1 beta (IL-1). The intracellular signals responsible for mediating the effects of IL-1 on MCP-1 expression in human mesangial cells have not been defined. Evidence from other types of cells suggests that protein kinases are involved in MCP-1 gene regulation. We investigated the role of protein kinase pathways in mediating IL-1-induced MCP-1 expression. Activation of protein kinase C (PKC) by phorbol esters or diacyglycerol up-regulated mesangial MCP-1 message and bioactivity in a fashion similar to IL-1. However, while inhibition of PKC activity completely blocked phorbol-induced MCP-1 up-regulation, induction by IL-1 was not prevented. Inhibitors of cyclic AMP (cAMP)-dependent protein kinase (PKA) also failed to block IL-1-induced MCP-1 expression. Furthermore, increasing intracellular cAMP and activating PKA attenuated basal MCP-1 mRNA levels by 82% and blocked IL-1 induced MCP-1 expression by 88%. Finally, the role of protein tyrosine kinases was studied. The structurally distinct protein tyrosine kinase (PTK) inhibitors genistein, herbimycin A, and tyrphostin each caused a dose-dependent inhibition of the effects of IL-1 on mesangial MCP-1 activity. IL-1 treatment of mesangial cells resulted in the up-regulation of three tyrosine phosphoproteins with apparent molecular masses between 40 and 62 kD. These results suggest that the effects of IL-1 on MCP-1 expression are not mediated through PKC or cAMP-PKA, but may be transduced through PTKs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Chemokine CCL2
  • Chemotactic Factors / biosynthesis*
  • Chemotactic Factors / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Gene Expression / drug effects
  • Glomerular Mesangium / drug effects*
  • Glomerular Mesangium / metabolism*
  • Humans
  • Interleukin-1 / pharmacology*
  • Protein Kinase C / metabolism
  • Protein Kinase Inhibitors
  • Protein Kinases / metabolism*
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • Chemokine CCL2
  • Chemotactic Factors
  • Interleukin-1
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C