PMID- 12060490
OWN - NLM
STAT- MEDLINE
DCOM- 20021204
LR  - 20181130
IS  - 1079-9907 (Print)
IS  - 1079-9907 (Linking)
VI  - 22
IP  - 5
DP  - 2002 May
TI  - Monocyte chemoattractant protein-1-induced activation of p42/44 MAPK and c-Jun in 
      murine peritoneal macrophages: a potential pathway for macrophage activation.
PG  - 517-26
AB  - The role of monocyte chemoattractant protein-1 (MCP-1) in mediating the 
      infiltration and activation of monocytes/macrophages into the sites of 
      inflammation or tumor growth is well documented, but the molecular mechanism(s) 
      involved in the process is poorly understood. In the current investigation, we 
      demonstrate activation of the p42/44 MAPK-mediated signal transduction in murine 
      peritoneal macrophages on stimulation with MCP-1 (10-100 ng/ml) in vitro. The 
      p42/44 MAPK activation was determined by studying the expression of the 
      phosphorylated p42/44 MAPK (Thr202/Tyr204) in the MCP-1-treated macrophages. This 
      response was found to be rapid and time dependent, detectable within 5 min of 
      MCP-1 stimulation. PD98058 (5-50 microM), a specific inhibitor of MAPK kinase 
      (MEK) inhibited the p42/44 MAPK phosphorylation, indicating the specificity of 
      the response. Furthermore, the MCP-1-induced phosphorylation of p42/44 MAPK was 
      found to be blocked by pertussis toxin (100 ng/ml), tyrosine kinase 
      inhibitor-genestein (10 ng/ml), PI3K inhibitor-wortmannin (20-200 microM), and 
      anti-CCR2 antibody (2.5 microg/ml). Additionally, phosphorylation of JNK and 
      activation of the transcription factor, c-Jun, were also noted in response to 
      MCP-1 treatment. Lastly, the MCP1-induced p42/44 MAPK activity was correlated 
      with the functional activation of macrophages by demonstrating the dose-specific 
      inhibition of actin polymerization, macrophage-mediated tumor cell cytotoxicity, 
      and tumor necrosis factor-alpha (TNF-alpha) transcription/production afforded by 
      PD98059 in the MCP-1-treated macrophages. Taken together, these data suggest the 
      involvement of the p42/44 MAPK/c-Jun pathway in the signal transduction process, 
      leading to activation of murine peritoneal macrophages.
FAU - Sodhi, Ajit
AU  - Sodhi A
AD  - School of Biotechnology, Banaras Hindu University, Varanasi 221005, India. 
      ajit.sodhi@lycos.com
FAU - Biswas, Subhra K
AU  - Biswas SK
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (Actins)
RN  - 0 (Androstadienes)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - DH2M523P0H (Genistein)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Actins/metabolism
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology
MH  - Chemokine CCL2/*pharmacology
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Genistein/pharmacology
MH  - In Vitro Techniques
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Macrophage Activation/drug effects
MH  - Macrophages, Peritoneal/*drug effects/immunology/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Pertussis Toxin/pharmacology
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-jun/*metabolism
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/antagonists & inhibitors
MH  - Signal Transduction/drug effects
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - Wortmannin
EDAT- 2002/06/13 10:00
MHDA- 2002/12/05 04:00
CRDT- 2002/06/13 10:00
PHST- 2002/06/13 10:00 [pubmed]
PHST- 2002/12/05 04:00 [medline]
PHST- 2002/06/13 10:00 [entrez]
AID - 10.1089/10799900252981990 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 2002 May;22(5):517-26. doi: 10.1089/10799900252981990.