Thrombin induces expression of cytokine-induced SH2 protein (CIS) in rat brain astrocytes: involvement of phospholipase A2, cyclooxygenase, and lipoxygenase

Glia
Kyung-Ae JiEun-Hye Joe

Abstract

Previously we have reported that thrombin induces inflammatory mediators in brain glial cells (Ryu et al. 2000. J Biol Chem 275:29955). In the present study, we found that thrombin induced a negative regulator of a cytokine signaling molecule, cytokine-induced SH2 protein (CIS), in rat brain astrocytes. In response to thrombin, CIS expression was increased at both the mRNA and protein levels. Although STAT5 is known to regulate CIS expression, thrombin did not activate STAT5, and inhibitors of JAK2 (AG490) and JAK3 (WHI-P97 and WHI-P154) had little effect on thrombin-induced CIS expression. In contrast, cytosolic phospholipase A(2) (cPLA(2)), cyclooxygenase (COX), and lipoxygenase (LO) play a role in CIS expression, since inhibitors of cPLA(2), cyclooxygenase (COX), and LO significantly reduced CIS expression. Reactive oxygen species (ROS) scavengers (N-acetyl-cysteine [NAC] and trolox) reduced thrombin-induced CIS expression, and inhibitors of COX and LO reduced ROS produced by thrombin. Furthermore, prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)), products of COX and LO, respectively, potentiated thrombin-induced CIS expression, indicating that ROS, and PGE(2) and LTB(4) generated by COX and LO, mediate CIS expressi...Continue Reading

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Citations

Jul 30, 2010·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Noriyuki ShibataMakio Kobayashi
Oct 22, 2010·Experimental & Molecular Medicine·Hey-Kyeong JeongEun-hye Joe
Mar 10, 2007·Journal of Neuroscience Research·Myung-Soon YangEunhye Joe
Apr 23, 2009·Neuroscience Letters·Lakshmi ThirumangalakudiPaula Grammas
May 8, 2018·Experimental Neurobiology·Eun-Hye JoeSangmyun Park
Nov 28, 2020·General and Comparative Endocrinology·Xintong LyuLan Wu
Jul 6, 2020·General and Comparative Endocrinology·Xintong LyuLan Wu

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