PMID- 7861699
OWN - NLM
STAT- MEDLINE
DCOM- 19950321
LR  - 20190725
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 46
IP  - 4
DP  - 1994 Oct
TI  - Role of protein kinase pathways in IL-1-induced chemoattractant expression by 
      human mesangial cells.
PG  - 1059-68
AB  - 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.
FAU - Rovin, B H
AU  - Rovin BH
AD  - Department of Medicine, Ohio State University School of Medicine, Columbus.
FAU - Tan, L C
AU  - Tan LC
LA  - eng
GR  - R29 DK46055/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemotactic Factors)
RN  - 0 (Interleukin-1)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2
MH  - Chemotactic Factors/*biosynthesis/genetics
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - Gene Expression/drug effects
MH  - Glomerular Mesangium/*drug effects/*metabolism
MH  - Humans
MH  - Interleukin-1/*pharmacology
MH  - Protein Kinase C/metabolism
MH  - Protein Kinase Inhibitors
MH  - Protein Kinases/*metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - RNA, Messenger/genetics/metabolism
EDAT- 1994/10/01 00:00
MHDA- 1994/10/01 00:01
CRDT- 1994/10/01 00:00
PHST- 1994/10/01 00:00 [pubmed]
PHST- 1994/10/01 00:01 [medline]
PHST- 1994/10/01 00:00 [entrez]
AID - S0085-2538(15)58648-1 [pii]
AID - 10.1038/ki.1994.367 [doi]
PST - ppublish
SO  - Kidney Int. 1994 Oct;46(4):1059-68. doi: 10.1038/ki.1994.367.