Dexamethasone suppresses interleukin-1β-induced human β-defensin 2 mRNA expression: involvement of p38 MAPK, JNK, MKP-1, and NF-κB transcriptional factor in A549 cells
In: FEMS Immunology & Medical Microbiology, Jg. 51 (2007-10-01), S. 171-184
Online
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Zugriff:
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.
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Dexamethasone suppresses interleukin-1β-induced human β-defensin 2 mRNA expression: involvement of p38 MAPK, JNK, MKP-1, and NF-κB transcriptional factor in A549 cells
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Autor/in / Beteiligte Person: | Jang, Byeong-Churl ; Suh, Seong-Il ; Lim, Ki-Jo ; Park, Jong-Gu ; Suh, Min-Ho |
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Zeitschrift: | FEMS Immunology & Medical Microbiology, Jg. 51 (2007-10-01), S. 171-184 |
Veröffentlichung: | Oxford University Press (OUP), 2007 |
Medientyp: | unknown |
ISSN: | 1574-695X (print) ; 0928-8244 (print) |
DOI: | 10.1111/j.1574-695x.2007.00293.x |
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