scholarly journals Involvement of Mitogen-Activated Protein Kinase Pathways in Interleukin-8 Production by Human Monocytes and Polymorphonuclear Cells Stimulated with Lipopolysaccharide or Mycoplasma fermentans Membrane Lipoproteins

1999 ◽  
Vol 67 (2) ◽  
pp. 688-693 ◽  
Author(s):  
Christelle Marie ◽  
Sergio Roman-Roman ◽  
Georges Rawadi
Keyword(s):  
Protein Kinase ◽  
Protein Tyrosine Kinase ◽  
Human Monocyte ◽  
Interleukin 8 ◽  
Mitogen Activated Protein Kinase ◽  
Polymorphonuclear Cells ◽  
Mycoplasma Fermentans ◽  
Downstream Signaling ◽  
Inflammatory Stimuli ◽  
Mitogen Activated Protein

ABSTRACT Interleukin-8 (IL-8) is a chemokine that belongs to the α-chemokine or CXC subfamily and is produced by a wide variety of human cells, including monocytes and polymorphonuclear cells (PMN). IL-8 is secreted in response to inflammatory stimuli, notably bacterial products such as lipopolysaccharide (LPS), but little is known about the mechanisms by which these agents mediate IL-8 induction. In this report, we show that Mycoplasma fermentans lipid-associated membrane proteins (LAMPf) induce the production of high levels of IL-8 by THP-1 (human monocyte) cells and PMN at the same extent as LPS. It was previously demonstrated that stimulation of monocytic cells with either LPS or LAMPf led to a series of common downstream signaling events, including the activation of protein tyrosine kinase and of mitogen-activated protein kinase cascades. By using PD-98059 and SB203580, two potent and selective inhibitors of MEK1 (a kinase upstream of ERK1/2) and p38, respectively, we have demonstrated that both ERK1/2 and p38 cascades play a key role in the production of IL-8 by monocytes and PMN stimulated with bacterial fractions.

scholarly journals Interleukin-8 Regulation of the Ras/Raf/Mitogen-activated Protein Kinase Pathway in Human Neutrophils

1996 ◽  
Vol 271 (5) ◽  
pp. 2832-2838 ◽  
Author(s):  
Cindy Knall ◽  
Scott Young ◽  
Jerry A. Nick ◽  
Anne Mette Buhl ◽  
G. Scott Worthen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Interleukin 8 ◽  
Mitogen Activated Protein Kinase ◽  
Human Neutrophils ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

scholarly journals Phosphorylation of the c-Fos transrepression domain by mitogen-activated protein kinase and 90-kDa ribosomal S6 kinase

1993 ◽  
Vol 90 (23) ◽  
pp. 10952-10956 ◽  
Author(s):  
R H Chen ◽  
C Abate ◽  
J Blenis
Keyword(s):  
Protein Kinase ◽  
Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
S6 Kinase ◽  
Downstream Signaling ◽  
C Terminus ◽  
Mitogen Activated Protein ◽  
Ribosomal S6 Kinase

Phosphorylation of the C terminus of c-Fos has been implicated in serum response element-mediated repression of c-fos transcription after its induction by serum growth factors. The growth-regulated enzymes responsible for this phosphorylation in early G1 phase of the cell cycle and the sites of phosphorylation have not been identified. We now provide evidence that two growth-regulated, nucleus- and cytoplasm-localized protein kinases, 90-kDa ribosomal S6 kinase (RSK) and mitogen-activated protein kinase (MAP kinase), contribute to the serum-induced phosphorylation of c-Fos. The major phosphopeptides derived from biosynthetically labeled c-Fos correspond to phosphopeptides generated after phosphorylation of c-Fos in vitro with both RSK and MAP kinase. The phosphorylation sites identified for RSK (Ser-362) and MAP kinase (Ser-374) are in the transrepression domain. Cooperative phosphorylation at these sites by both enzymes was observed in vitro and reflected in vivo by the predominance of the peptide phosphorylated on both sites, as opposed to singly phosphorylated peptides. This study suggests a role for nuclear RSK and MAP kinase in modulating newly synthesized c-Fos phosphorylation and downstream signaling.

scholarly journals Embelin as a Novel Inhibitor of PKC in the Prevention of Platelet Activation and Thrombus Formation

2019 ◽  
Vol 8 (10) ◽  
pp. 1724 ◽  
Author(s):  
Jiun Yi Li ◽  
Ray Jade Chen ◽  
Li Ting Huang ◽  
Tzu Yin Lee ◽  
Wan Jung Lu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Therapeutic Potential ◽  
Thrombus Formation ◽  
Biological Activities ◽  
Mitogen Activated Protein Kinase ◽  
Antitumor Effects ◽  
Pkc Inhibitor ◽  
Downstream Signaling ◽  
Embelia Ribes ◽  
Mitogen Activated Protein

Embelin is a quinone derivative and found in the fruits of Embelia ribes Burm.f. Embelin has been identified as a small molecular inhibitor of X-chromosome-linked inhibitor of apoptosis proteins, and has multiple biological activities, including antioxidation, anti-inflammation, and antitumor effects. However, the effect of embelin in platelets remains unclear. Thus, this study investigated the antiplatelet mechanism of embelin. Our data revealed that embelin could inhibit platelet aggregation induced by various agonists, including the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBu). Embelin, as well as the PKC inhibitor Ro 31-8220, markedly reduced PDBu-mediated phosphorylation of the PKC substrate, suggesting that embelin may be a PKC inhibitor for platelets. Embelin could block PKC downstream signaling and events, including the inhibition of protein kinase B and mitogen-activated protein kinase activation, granule release, and glycoprotein IIbIIIa activation. Moreover, embelin could delay thrombus formation in the mesenteric microvessels of mice, but did not significantly affect the tail bleeding time. In conclusion, we demonstrated that embelin is a PKC inhibitor and possesses antiplatelet and antithrombotic effects. The further analysis is necessary to more accurately determine clinical therapeutic potential of embelin in all clinical thromboembolic events with disturbance of thrombocyte function.

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