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Infection and Immunity, February 1999, p. 688-693, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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

Christelle Marie,1 Sergio Roman-Roman,2 and Georges Rawadi3,*

Unité d'Immuno-Allergie1 and Département de Bactériologie et de Mycologie, Laboratoire des Mycoplasmes,2 Paris 75724 Cedex 15, and Centre de Recherche Romainville, Hoechst-Marion-Roussel, 93230 Romainville Cedex,3 France

Received 27 October 1998/Accepted 19 November 1998

Interleukin-8 (IL-8) is a chemokine that belongs to the alpha -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.

* Corresponding author. Mailing address: Hoechst Marion Roussel, Anti-infectious Group, 102 route de Noisy, 93235 Romainville Cedex, France. Phone: 33-1-49916199. Fax: 33-1-49916380. E-mail: Georges.Rawadi{at}hmrag.com.

Infection and Immunity, February 1999, p. 688-693, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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