Sphingosine-1-phosphate mediates ICAM-1-dependent monocyte adhesion through p38 MAPK and p42/p44 MAPK-dependent Akt activation

PloS One
Chih-Chung LinChuen-Mao Yang

Abstract

Up-regulation of intercellular adhesion molecule-1 (ICAM-1) is frequently implicated in lung inflammation. Sphingosine-1-phosphate (S1P) has been shown to play a key role in inflammation via adhesion molecules induction, and then causes lung injury. However, the mechanisms underlying S1P-induced ICAM-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unclear. The effect of S1P on ICAM-1 expression was determined by Western blot and real-time PCR. The involvement of signaling pathways in these responses was investigated by using the selective pharmacological inhibitors and transfection with siRNAs. S1P markedly induced ICAM-1 expression and monocyte adhesion which were attenuated by pretreatment with the inhibitor of S1PR1 (W123), S1PR3 (CAY10444), c-Src (PP1), EGFR (AG1478), PDGFR (AG1296), MEK1/2 (U0126), p38 MAPK (SB202190), JNK1/2 (SP600125), PI3K (LY294002), or AP-1 (Tanshinone IIA) and transfection with siRNA of S1PR1, S1PR3, c-Src, EGFR, PDGFR, p38, p42, JNK1, c-Jun, or c-Fos. We observed that S1P-stimulated p42/p44 MAPK and p38 MAPK activation was mediated via a c-Src/EGFR and PDGFR-dependent pathway. S1P caused the c-Src/EGFR/PDGFR complex formation. On the other hand, we demonstrated that S1P i...Continue Reading

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Citations

Sep 13, 2015·Molecular and Cellular Endocrinology·Haijiang WuHuijun Duan
Jan 10, 2018·Journal of Neurotrauma·Salvatore CuzzocreaDaniela Salvemini
Jan 7, 2018·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·J MaJ Du
Sep 25, 2017·Oncotarget·Gabriela SchneiderMariusz Z Ratajczak
Sep 23, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Fang LiCungui Mao
Sep 26, 2020·Frontiers in Cellular Neuroscience·Mari Paz Serrano-RegalMaría Victoria Sánchez-Gómez
Mar 7, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Katarzyna Bocheńska, Magdalena Gabig-Cimińska
Feb 28, 2018·International Journal of Molecular Medicine·Mengda CaoJi-Fu Wei

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Methods Mentioned

BETA
transfection
PCR
electrophoresis
immunoprecipitation

Software Mentioned

GraphPad Prism

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