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Dexamethasone suppresses interleukin-1beta-induced human beta-defensin 2 mRNA expression: involvement of p38 MAPK, JNK, MKP-1, and NF-kappaB transcriptional factor in A549 cells.
FEMS Immunol Med Microbiol. 2007 Oct; 51(1):171-84.FI

Abstract

Human beta-defensin (HBD)-2 is an inducible antimicrobial peptide that plays an important role in innate immunity. Glucocorticoids, on the other hand, exert immunosuppressive and anti-inflammatory actions. We have previously reported that interleukin (IL)-1beta induces HBD-2 mRNA expression through the activation of nuclear factor-kappaB (NF-kappaB) transcriptional factor, as well as p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), or phosphatidylinositol-3-kinase/AKT in A549 cells. In this study, we further investigated whether dexamethasone (Dex) controls IL-1beta-induced HBD-2 mRNA expression in A549 cells and the molecular mechanism associated with it. Dex suppressed IL-1beta-induced HBD-2 mRNA expression, which is mediated by a glucocorticoid receptor, at the transcriptional level. Interestingly, Dex attenuated IL-1beta-mediated activation of p38 MAPK and JNK, but not of AKT. Dex increased the expression of MAPK phosphatase (MKP)-1, which dephosphorylated p38 MAPK, but not JNK, by IL-1beta. However, although Dex did not inhibit the nuclear translocation of p65 NF-kappaB in response to IL-1beta, it profoundly inhibited NF-kappaB promoter- and HBD-2 promoter-driven luciferase activities. These results suggest that Dex acts to inhibit IL-1beta-induced HBD-2 mRNA expression through blockage of the nuclear transcriptional activation of p65 NF-kappaB as well as through inactivation of p38 MAPK and JNK. Specifically, Dex-induced MKP-1 expression is responsible for the inactivation of p38 MAPK, but not JNK, in response to IL-1beta in A549 cells.

Authors+Show Affiliations

Chronic Disease Research Center and Institute for Medical Science, School of Medicine Keimyung University, Daegu, Korea.No 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

17645739

Citation

Jang, Byeong-Churl, et al. "Dexamethasone Suppresses Interleukin-1beta-induced Human Beta-defensin 2 mRNA Expression: Involvement of P38 MAPK, JNK, MKP-1, and NF-kappaB Transcriptional Factor in A549 Cells." FEMS Immunology and Medical Microbiology, vol. 51, no. 1, 2007, pp. 171-84.
Jang BC, Lim KJ, Suh MH, et al. Dexamethasone suppresses interleukin-1beta-induced human beta-defensin 2 mRNA expression: involvement of p38 MAPK, JNK, MKP-1, and NF-kappaB transcriptional factor in A549 cells. FEMS Immunol Med Microbiol. 2007;51(1):171-84.
Jang, B. C., Lim, K. J., Suh, M. H., Park, J. G., & Suh, S. I. (2007). Dexamethasone suppresses interleukin-1beta-induced human beta-defensin 2 mRNA expression: involvement of p38 MAPK, JNK, MKP-1, and NF-kappaB transcriptional factor in A549 cells. FEMS Immunology and Medical Microbiology, 51(1), 171-84.
Jang BC, et al. Dexamethasone Suppresses Interleukin-1beta-induced Human Beta-defensin 2 mRNA Expression: Involvement of P38 MAPK, JNK, MKP-1, and NF-kappaB Transcriptional Factor in A549 Cells. FEMS Immunol Med Microbiol. 2007;51(1):171-84. PubMed PMID: 17645739.
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TY - JOUR T1 - Dexamethasone suppresses interleukin-1beta-induced human beta-defensin 2 mRNA expression: involvement of p38 MAPK, JNK, MKP-1, and NF-kappaB transcriptional factor in A549 cells. AU - Jang,Byeong-Churl, AU - Lim,Ki-Jo, AU - Suh,Min-Ho, AU - Park,Jong-Gu, AU - Suh,Seong-Il, Y1 - 2007/07/23/ PY - 2007/7/25/pubmed PY - 2007/11/6/medline PY - 2007/7/25/entrez SP - 171 EP - 84 JF - FEMS immunology and medical microbiology JO - FEMS Immunol Med Microbiol VL - 51 IS - 1 N2 - Human beta-defensin (HBD)-2 is an inducible antimicrobial peptide that plays an important role in innate immunity. Glucocorticoids, on the other hand, exert immunosuppressive and anti-inflammatory actions. We have previously reported that interleukin (IL)-1beta induces HBD-2 mRNA expression through the activation of nuclear factor-kappaB (NF-kappaB) transcriptional factor, as well as p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), or phosphatidylinositol-3-kinase/AKT in A549 cells. In this study, we further investigated whether dexamethasone (Dex) controls IL-1beta-induced HBD-2 mRNA expression in A549 cells and the molecular mechanism associated with it. Dex suppressed IL-1beta-induced HBD-2 mRNA expression, which is mediated by a glucocorticoid receptor, at the transcriptional level. Interestingly, Dex attenuated IL-1beta-mediated activation of p38 MAPK and JNK, but not of AKT. Dex increased the expression of MAPK phosphatase (MKP)-1, which dephosphorylated p38 MAPK, but not JNK, by IL-1beta. However, although Dex did not inhibit the nuclear translocation of p65 NF-kappaB in response to IL-1beta, it profoundly inhibited NF-kappaB promoter- and HBD-2 promoter-driven luciferase activities. These results suggest that Dex acts to inhibit IL-1beta-induced HBD-2 mRNA expression through blockage of the nuclear transcriptional activation of p65 NF-kappaB as well as through inactivation of p38 MAPK and JNK. Specifically, Dex-induced MKP-1 expression is responsible for the inactivation of p38 MAPK, but not JNK, in response to IL-1beta in A549 cells. SN - 0928-8244 UR - https://www.unboundmedicine.com/medline/citation/17645739/Dexamethasone_suppresses_interleukin_1beta_induced_human_beta_defensin_2_mRNA_expression:_involvement_of_p38_MAPK_JNK_MKP_1_and_NF_kappaB_transcriptional_factor_in_A549_cells_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0928-8244&date=2007&volume=51&issue=1&spage=171 DB - PRIME DP - Unbound Medicine ER -