title: Up-regulation of human beta-defensin 2 by interleukin-1beta in A549 cells: involvement of PI3K, PKC, p38 MAPK, JNK, and NF-kappaB.
abstract: Induction of human beta-defensin 2 (HBD-2) by interleukin-1beta (IL-1beta) in epithelial cells has been reported. However, the mechanism by which IL-1beta up-regulates HBD-2 remains poorly understood. In this study, we investigated the effect of IL-1beta on induction of HBD-2 in A549 cells. IL-1beta markedly increased HBD-2 mRNA expression in concentration- and time-dependent manners. HBD-2 mRNA expression in response to IL-1beta was attenuated by pretreatment of GF109203X, Go6976, and staurosporine [inhibitors of protein kinase C (PKC)], SB203580 [an inhibitor of p38 mitogen-activated protein kinase (MAPK)], SP600125 [an inhibitor of c-Jun N-terminal kinase (JNK)], and LY294002 [an inhibitor of phosphatidylinositol-3-kinase (PI3K)], but not PD98059 [an inhibitor of extracellular signal-regulated kinase (ERK)], suggesting involvement of PKC, p38 MAPK, JNK, and PI3K in this response. Interestingly, IL-1beta induced nuclear factor-kappaB (NF-kappaB) activation in A549 cells, which was shown by increased nuclear translocation of p65 NF-kappaB and degradation of IkappaB-alpha. Importantly, IL-1beta-induced HBD-2 mRNA expression was inhibited by blockage of NF-kappaB activation using NF-kappaB inhibitors, including pyrrolidine dithiocarbamate and MG132. Specifically, IL-1beta-induced nuclear translocation of NF-kappaB was in part attenuated by LY294002, but not by GF109203X, SB203580, and SP600125, suggesting PI3K-dependent nuclear translocation of NF-kappaB in response to IL-1beta. Together, these results suggest that IL-1beta induces HBD-2 mRNA expression in A549 cells, and the induction seems to be at least in part mediated through activation of NF-kappaB transcription factor as well as activation of signaling proteins of PKC, p38 MAPK, JNK, and PI3K, but not ERK.
authors.affiliation: Department of Microbiology, Chronic Disease Research Center, Institute for Medical Science, School of Medicine, Keimyung University, #194 DongSan-Dong Jung-Gu, Daegu 700-712, Republic of Korea.
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
authors.forename: Ki-Jo
authors.initials: KJ
authors.lastname: Lim
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Paik
authors.forename: Young-Kyu
authors.initials: YK
authors.lastname: Kwon
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Shin
authors.forename: Sang-Chan
authors.initials: SC
authors.lastname: Kim
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Jung
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
authors.forename: Jae-We
authors.initials: JW
authors.lastname: Cho
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Baek
authors.forename: Sang-Pyo
authors.initials: SP
authors.lastname: Kim
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Suh
authors.forename: Seong-Il
authors.initials: SI
authors.lastname: Suh
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: C106641:DEFB4A protein, human; D007375:Interleukin-1; D016328:NF-kappa B; D023083:beta-Defensins; D010770:Phosphotransferases