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Triptolide suppresses interleukin-1beta-induced human beta-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-kappaB in A549 cells.
Int J Mol Med. 2007 May; 19(5):757-63.IJ

Abstract

The immunosuppressive effect of triptolide has been associated with suppression of T-cell activation. However, the immunosuppressive effects of triptolide on innate immunity in the epithelial barrier remain to be elucidated. Human beta-defensin (HBD)-2 is an inducible antimicrobial peptide and plays an important role in the innate immunity. We have previously demonstrated that IL-1beta induced HBD-2 mRNA expression in A549 cells through 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 (PI3K). In this study, we investigated effects of triptolide on IL-1beta-induced HBD-2 mRNA expression in A549 cells. Triptolide inhibited IL-1beta-induced HBD-2 mRNA expression in a dose-dependent manner. Addition of triptolide did not suppress activation of p38 MAPK, JNK, or PI3K in response to IL-1beta. Triptolide inhibited IL-1beta-induced MAPK phosphatase-1 expression at the transcriptional level and resulted in sustained phosphorylation of JNK or p38 MAPK, explaining the little effect of triptolide on IL-1beta-induced phosphorylation of these kinases. Although triptolide partially suppressed IL-1beta-mediated degradation of IkappaB-alpha and nuclear translocation of p65 NF-kappaB, triptolide potently inhibited NF-kappaB promoter-driven luciferase activity in A549 cells. These results collectively suggest that the inhibitory effect of triptolide on IL-1beta-induced HBD-2 mRNA expression in A549 cells seems to be at least in part mediated through nuclear inhibition of NF-kappaB transcriptional activity, but not inhibition of p38 MAPK, JNK, or PI3K. This inhibition may explain the ability of triptolide to diminish innate immune response.

Authors+Show Affiliations

Chronic Disease Research Center and Institute for Medical Science, Keimyung University School of Medicine, Daegu, 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 available

Pub Type(s)

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

Language

eng

PubMed ID

17390080

Citation

Jang, Byeong-Churl, et al. "Triptolide Suppresses Interleukin-1beta-induced Human Beta-defensin-2 mRNA Expression Through Inhibition of Transcriptional Activation of NF-kappaB in A549 Cells." International Journal of Molecular Medicine, vol. 19, no. 5, 2007, pp. 757-63.
Jang BC, Lim KJ, Choi IH, et al. Triptolide suppresses interleukin-1beta-induced human beta-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-kappaB in A549 cells. Int J Mol Med. 2007;19(5):757-63.
Jang, B. C., Lim, K. J., Choi, I. H., Suh, M. H., Park, J. G., Mun, K. C., Bae, J. H., Shin, D. H., & Suh, S. I. (2007). Triptolide suppresses interleukin-1beta-induced human beta-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-kappaB in A549 cells. International Journal of Molecular Medicine, 19(5), 757-63.
Jang BC, et al. Triptolide Suppresses Interleukin-1beta-induced Human Beta-defensin-2 mRNA Expression Through Inhibition of Transcriptional Activation of NF-kappaB in A549 Cells. Int J Mol Med. 2007;19(5):757-63. PubMed PMID: 17390080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Triptolide suppresses interleukin-1beta-induced human beta-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-kappaB in A549 cells. AU - Jang,Byeong-Churl, AU - Lim,Ki-Jo, AU - Choi,In-Hak, AU - Suh,Min-Ho, AU - Park,Jong-Gu, AU - Mun,Kyo-Chul, AU - Bae,Jae-Hoon, AU - Shin,Dong-Hoon, AU - Suh,Seong-Il, PY - 2007/3/29/pubmed PY - 2007/5/19/medline PY - 2007/3/29/entrez SP - 757 EP - 63 JF - International journal of molecular medicine JO - Int J Mol Med VL - 19 IS - 5 N2 - The immunosuppressive effect of triptolide has been associated with suppression of T-cell activation. However, the immunosuppressive effects of triptolide on innate immunity in the epithelial barrier remain to be elucidated. Human beta-defensin (HBD)-2 is an inducible antimicrobial peptide and plays an important role in the innate immunity. We have previously demonstrated that IL-1beta induced HBD-2 mRNA expression in A549 cells through 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 (PI3K). In this study, we investigated effects of triptolide on IL-1beta-induced HBD-2 mRNA expression in A549 cells. Triptolide inhibited IL-1beta-induced HBD-2 mRNA expression in a dose-dependent manner. Addition of triptolide did not suppress activation of p38 MAPK, JNK, or PI3K in response to IL-1beta. Triptolide inhibited IL-1beta-induced MAPK phosphatase-1 expression at the transcriptional level and resulted in sustained phosphorylation of JNK or p38 MAPK, explaining the little effect of triptolide on IL-1beta-induced phosphorylation of these kinases. Although triptolide partially suppressed IL-1beta-mediated degradation of IkappaB-alpha and nuclear translocation of p65 NF-kappaB, triptolide potently inhibited NF-kappaB promoter-driven luciferase activity in A549 cells. These results collectively suggest that the inhibitory effect of triptolide on IL-1beta-induced HBD-2 mRNA expression in A549 cells seems to be at least in part mediated through nuclear inhibition of NF-kappaB transcriptional activity, but not inhibition of p38 MAPK, JNK, or PI3K. This inhibition may explain the ability of triptolide to diminish innate immune response. SN - 1107-3756 UR - https://www.unboundmedicine.com/medline/citation/17390080/Triptolide_suppresses_interleukin_1beta_induced_human_beta_defensin_2_mRNA_expression_through_inhibition_of_transcriptional_activation_of_NF_kappaB_in_A549_cells_ L2 - http://www.spandidos-publications.com/ijmm/19/5/757 DB - PRIME DP - Unbound Medicine ER -