Tec kinases regulate actin assembly and cytokine expression in LPS-stimulated human neutrophils via JNK activation.
The acute inflammatory response involves neutrophils wherein recognition of bacterial products, such as lipopolysaccharide (LPS), activates intracellular signaling pathways. We have shown that the mitogen-activated protein kinase (MAPK) c-Jun NH(2) terminal kinase (JNK) is activated by LPS in neutrophils and plays a critical role in monocyte chemoattractant protein (MCP)-1 expression and actin assembly. As the Tec family kinases are expressed in neutrophils and regulate activation of the MAPKs in other cell systems, we hypothesized that the Tec kinases are an upstream component of the signaling pathway leading to LPS-induced MAPKs activation in neutrophils. Herein, we show that the Tec kinases are activated in LPS-stimulated human neutrophils and that inhibition of the Tec kinases, with leflunomide metabolite analog (LFM-A13), decreased LPS-induced JNK, but not p38, activity. Furthermore, LPS-induced actin polymerization as well as MCP-1, tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta expression are dependent on Tec kinase activity.
Zemans
Rachel L
RL
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Colorado School of Medicine, Denver, CO 80206, USA.
Arndt
Patrick G
PG
D000199:Actins / Q000502:physiology*; D000577:Amides / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism
D000199:Actins; D000577:Amides; D018932:Chemokine CCL2; D016207:Cytokines; C118451:LFM A13; D008070:Lipopolysaccharides; D009570:Nitriles; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases