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Up-regulation of human beta-defensin 2 by interleukin-1beta in A549 cells: involvement of PI3K, PKC, p38 MAPK, JNK, and NF-kappaB.
Biochem Biophys Res Commun. 2004 Jul 30; 320(3):1026-33.BB

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+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15240151

Citation

Jang, Byeong-Churl, et al. "Up-regulation of Human Beta-defensin 2 By Interleukin-1beta in A549 Cells: Involvement of PI3K, PKC, P38 MAPK, JNK, and NF-kappaB." Biochemical and Biophysical Research Communications, vol. 320, no. 3, 2004, pp. 1026-33.
Jang BC, Lim KJ, Paik JH, et al. Up-regulation of human beta-defensin 2 by interleukin-1beta in A549 cells: involvement of PI3K, PKC, p38 MAPK, JNK, and NF-kappaB. Biochem Biophys Res Commun. 2004;320(3):1026-33.
Jang, B. C., Lim, K. J., Paik, J. H., Kwon, Y. K., Shin, S. W., Kim, S. C., Jung, T. Y., Kwon, T. K., Cho, J. W., Baek, W. K., Kim, S. P., Suh, M. H., & Suh, S. I. (2004). Up-regulation of human beta-defensin 2 by interleukin-1beta in A549 cells: involvement of PI3K, PKC, p38 MAPK, JNK, and NF-kappaB. Biochemical and Biophysical Research Communications, 320(3), 1026-33.
Jang BC, et al. Up-regulation of Human Beta-defensin 2 By Interleukin-1beta in A549 Cells: Involvement of PI3K, PKC, P38 MAPK, JNK, and NF-kappaB. Biochem Biophys Res Commun. 2004 Jul 30;320(3):1026-33. PubMed PMID: 15240151.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Up-regulation of human beta-defensin 2 by interleukin-1beta in A549 cells: involvement of PI3K, PKC, p38 MAPK, JNK, and NF-kappaB. AU - Jang,Byeong-Churl, AU - Lim,Ki-Jo, AU - Paik,Ji-Hye, AU - Kwon,Young-Kyu, AU - Shin,Sang-Woo, AU - Kim,Sang-Chan, AU - Jung,Tae-Young, AU - Kwon,Taeg Kyu, AU - Cho,Jae-We, AU - Baek,Won-Ki, AU - Kim,Sang-Pyo, AU - Suh,Min-Ho, AU - Suh,Seong-Il, PY - 2004/06/01/received PY - 2004/7/9/pubmed PY - 2004/8/27/medline PY - 2004/7/9/entrez SP - 1026 EP - 33 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 320 IS - 3 N2 - 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. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/15240151/Up_regulation_of_human_beta_defensin_2_by_interleukin_1beta_in_A549_cells:_involvement_of_PI3K_PKC_p38_MAPK_JNK_and_NF_kappaB_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006291X04013300 DB - PRIME DP - Unbound Medicine ER -