EGF Receptor-Dependent Mechanism May be Involved in the Tamm–Horsfall Glycoprotein-Enhanced PMN Phagocytosis via Activating Rho Family and MAPK Signaling Pathway
| Autor: | Song-Chou Hsieh, Chia-Li Yu, Chang-Youh Tsai, Cheng-Han Wu, Sue-Cien Siao, Ko-Jen Li, Chieh-Yu Shen, Tsai-Hung Wu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
MAPK/ERK pathway
Lipopolysaccharides rho GTP-Binding Proteins MAP Kinase Signaling System Neutrophils Phagocytosis Rho family Pharmaceutical Science p38 Mitogen-Activated Protein Kinases Article Analytical Chemistry lcsh:QD241-441 lcsh:Organic chemistry Drug Discovery Uromodulin Humans Protein Interaction Domains and Motifs Physical and Theoretical Chemistry Phosphorylation Receptor PI3K/AKT/mTOR pathway biology Organic Chemistry phagocytosis hemic and immune systems Cell biology Enzyme Activation ErbB Receptors Chemistry (miscellaneous) EGF-like domains Mitogen-activated protein kinase biology.protein Molecular Medicine lipids (amino acids peptides and proteins) MAP kinase Signal transduction Tamm-Horsfall glycoprotein Intracellular |
| Zdroj: | Molecules Molecules, Vol 19, Iss 1, Pp 1328-1343 (2014) Volume 19 Issue 1 Pages 1328-1343 |
| ISSN: | 1420-3049 |
| Popis: | Our previous studies showed that urinary Tamm–Horsfall glycoprotein (THP) potently enhanced polymorphonuclear neutrophil (PMN) phagocytosis. However, the domain structure(s), signaling pathway and the intracellular events responsible for THP-enhanced PMN phagocytosis remain to be elucidated. THP was purified from normal human urine. The human promyelocytic leukemia cell line HL-60 was induced to differentiate into PMNs by all-trans retinoid acid. Pretreatment with different MAPK and PI3K inhibitors was used to delineate signaling pathways in THP-enhanced PMN phagocytosis. Phosphorylation of molecules responsible for PMN phagocytosis induced by bacterial lipopolysaccharide (LPS), THP, or human recombinant epidermal growth factor (EGF) was evaluated by western blot. A p38 MAPK inhibitor, SB203580, effectively inhibited both spontaneous and LPS- and THP-induced PMN phagocytosis. Both THP and LPS enhanced the expression of the Rho family proteins Cdc42 and Rac that may lead to F-actin re-arrangement. Further studies suggested that THP and EGF enhance PMN and differentiated HL-60 cell phagocytosis in a similar pattern. Furthermore, the EGF receptor inhibitor GW2974 significantly suppressed THP- and EGF-enhanced PMN phagocytosis and p38 and ERK1/2 phosphorylation in differentiated HL-60 cells. We conclude that EGF receptor-dependent signaling may be involved in THP-enhanced PMN phagocytosis by activating Rho family and MAP kinase. |
| Databáze: | OpenAIRE |
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