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

Autor: Minho Shong, Kyung-Ae Ji, Eun-Hye Joe, Ilo Jou, Myung-Soon Yang
Rok vydání: 2004
Předmět:
medicine.medical_specialty
medicine.medical_treatment
Leukotriene Production
Lipoxygenase
Prostaglandin
Suppressor of Cytokine Signaling Proteins
Leukotriene B4
Dinoprostone
Phospholipases A
Immediate-Early Proteins
Rats
Sprague-Dawley
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Interferon-gamma
Thrombin
Phospholipase A2
Internal medicine
medicine
Animals
RNA
Messenger
Enzyme Inhibitors
Cells
Cultured
Feedback
Physiological
biology
Free Radical Scavengers
Molecular biology
Rats
Up-Regulation
DNA-Binding Proteins
Phospholipases A2
Endocrinology
STAT1 Transcription Factor
Neurology
chemistry
Animals
Newborn
Prostaglandin-Endoperoxide Synthases
Astrocytes
biology.protein
Trans-Activators
Encephalitis
Cyclooxygenase
Signal transduction
Inflammation Mediators
medicine.drug
Prostaglandin E
Zdroj: Glia. 48(2)
ISSN: 0894-1491
Popis: 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 expression. Since interferon-gamma (IFN-gamma)-induced GAS-luciferase activity and tyrosine phosphorylation of STAT1 and STAT3 were lower in CIS-transfected cells compared to control vector-transfected cells, CIS could have anti-inflammatory activity. These data suggest that thrombin-stimulation of ROS and prostaglandin and leukotriene production via the cPLA(2), COX and LO pathways results in CIS expression. More importantly, CIS expression may be a negative feedback mechanism that prevents prolonged inflammatory responses.
Databáze: OpenAIRE
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