fMLP-dependent activation of Akt and ERK1/2 through ROS/Rho A pathways is mediated through restricted activation of the FPRL1 (FPR2) receptor

Objective and design The objective of this study is to uncover the signal transduction pathways of N -formyl methionyl-leucyl-phenylalanine (fMLP) in monocyte. Materials or subjects Freshly isolated human peripheral blood monocytes (PBMC) were used for in vitro assessment of signal transduction path...

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Bibliographic Details
Published in:Inflammation research 2018-08, Vol.67 (8), p.711-722
Main Authors: Faour, Wissam H., Fayyad-Kazan, Hussein, El Zein, Nabil
Format: Article
Language:English
Subjects:
AKT protein
Allergology
Biomedical and Life Sciences
Biomedicine
Calcium
Calcium (intracellular)
CD11b antigen
Cell activation
Dermatology
Epidermal growth factor receptors
Extracellular signal-regulated kinase
Formyl peptides
Guanosine triphosphatases
Hydrogen peroxide
Immunology
Intracellular
Intracellular signalling
Kinases
Monocytes
Neurology
Original Research Paper
Peripheral blood mononuclear cells
Pharmacology/Toxicology
Phenylalanine
Rheumatology
RhoA protein
Signal transduction
siRNA
Spectrometry
Stimulators
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Summary:Objective and design The objective of this study is to uncover the signal transduction pathways of N -formyl methionyl-leucyl-phenylalanine (fMLP) in monocyte. Materials or subjects Freshly isolated human peripheral blood monocytes (PBMC) were used for in vitro assessment of signal transduction pathways activated by fMLP. Treatment Time-course and dose–response experiments were used to evaluate the effect of fMLP along with the specific inhibitors/stimulators on the activation of downstream signaling kinases. Methods Freshly isolated human PBMC were stimulated with fMLP for the desired time. Western blot and siRNA analysis were used to evaluate the activated intracellular signaling kinases, and flow analysis was performed to assess the levels of CD11b. Furthermore, luminescence spectrometry was performed to measure the levels of released hydrogen peroxide in the media. Results fMLP strongly stimulated the activation of AKT and ERK1/2 through a RhoA-GTPase-dependent manner and also induced H 2 O 2 release by monocytes. Furthermore, fMLP mediated its effects through restricted activation of formylpeptide receptor-like 1 (FPRL1/FPR2), but independently of either EGFR transactivation or intracellular calcium release. In addition, NAC reversed fMLP- and H 2 O 2 -induced activation of Akt and RhoA-GTPase. Conclusion Collectively, these data suggested that fMLP-activated ERK1/2 and Akt pathways through specific activation of the FPRL1/ROS/RoA-GTPase pathway.
ISSN:1023-3830
1420-908X
DOI:10.1007/s00011-018-1163-6