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Title: Interleukin-1-induced iNOS expression in human lung carcinoma A549 cells: Involvement of STAT and MAPK pathways
Authors: Ravichandran, Kameswaran
Tyagi, Alpna
Deep, Gagan
Agarwal, Chapla
Agarwal, Rajesh
Keywords: Human lung carcinoma;iNOS;Interleukin-1;MAPK;STAT
Issue Date: Nov-2011
Publisher: NISCAIR-CSIR, India
Abstract: For understanding of signaling molecules important in lung cancer growth and progression, IL-1 effect was analyzed on iNOS expression and key signaling molecules in human lung carcinoma A549 cells and established the role of specific signaling molecules by using specific chemical inhibitors. IL-1 exposure (10 ng/ml) induced strong iNOS expression in serum starved A549 cells. Detailed molecular analyses showed that IL-1 increased expression of phosphorylated STAT1 (Tyr701 and Ser727) and STAT3 (Tyr705 and Ser727) both in total cell lysates and nuclear lysates. Further, IL-1b exposure strongly activated MAPKs (ERK1/2, JNK1/2 and p38) and Akt as well as increased nuclear levels of NF-κB and HIF-1 in A549 cells. Use of specific chemical inhibitors for JAK1 kinase (piceatannol), JAK2 kinase (AG-490), MEK1/2 (PD98059) and JNK1/2 (SP600125) revealed that IL-1-induced iNOS expression involved signaling pathways in addition to JAK-STAT and ERK1/2-JNK1/2 activation. Overall, these results suggested that instead of specific pharmacological inhibitors, use of chemopreventive agents with broad spectrum efficacy to inhibit IL-1-induced signaling cascades and iNOS expression would be a better strategy towards lung cancer prevention and/or treatment.
Page(s): 840-847
ISSN: 0975-1009 (Online); 0019-5189 (Print)
Appears in Collections:IJEB Vol.49(11) [November 2011]

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