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Involvement of p42/p44 MAPK, p38 MAPK, JNK and nuclear factor-kappa B in interleukin-1beta-induced matrix metalloproteinase-9 expression in rat brain astrocytes.
J Neurochem. 2004 Sep; 90(6):1477-88.JN

Abstract

Matrix metalloproteinase (MMP)-9 expression induced by interleukin-1beta (IL-1beta) was investigated in rat brain astrocyte-1 (RBA-1). Here we report that the mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kappaB) pathways participate in the induction of MMP-9 expression by IL-1beta. Zymographic, western blotting, and RT-PCR analyses showed that IL-1beta increased expression of MMP-9 mRNA and protein, which were inhibited by inhibitors of MEK1/2 (U0126), p38 (SB202190), and JNK (SP600125). In accordance with these findings, IL-1beta stimulated phosphorylation of p42/p44 MAPK, p38, and c-Jun N-terminal kinase (JNK), which was attenuated by U0126, SB202190, or SP600125, respectively. Furthermore, this up-regulation of MMP-9 mRNA and protein was blocked by a specific NF-kappaB inhibitor helenalin. Consistently, IL-1beta-stimulated translocation of NF-kappaB into the nucleus and degradation of inhibitory kappa B-alpha (IkappaB-alpha) was revealed by western blotting and immunofluorescence staining, which was blocked by helenalin, but not by U0126, SB202190, or SP600125. Taken together, these results suggest that in RBA-1 cells, activation of p42/p44 MAPK, p38, JNK and NF-kappaB pathways is essential for IL-1beta-induced MMP-9 gene expression via transcription and translation processes. An increased understanding of the signal transduction pathways involved in IL-1beta-induced MMP-9 expression on RBA-1 may be of potential therapeutic value in the treatment of inflammatory disease.

Authors+Show Affiliations

Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15341531

Citation

Wu, Cheng-Ying, et al. "Involvement of P42/p44 MAPK, P38 MAPK, JNK and Nuclear Factor-kappa B in Interleukin-1beta-induced Matrix Metalloproteinase-9 Expression in Rat Brain Astrocytes." Journal of Neurochemistry, vol. 90, no. 6, 2004, pp. 1477-88.
Wu CY, Hsieh HL, Jou MJ, et al. Involvement of p42/p44 MAPK, p38 MAPK, JNK and nuclear factor-kappa B in interleukin-1beta-induced matrix metalloproteinase-9 expression in rat brain astrocytes. J Neurochem. 2004;90(6):1477-88.
Wu, C. Y., Hsieh, H. L., Jou, M. J., & Yang, C. M. (2004). Involvement of p42/p44 MAPK, p38 MAPK, JNK and nuclear factor-kappa B in interleukin-1beta-induced matrix metalloproteinase-9 expression in rat brain astrocytes. Journal of Neurochemistry, 90(6), 1477-88.
Wu CY, et al. Involvement of P42/p44 MAPK, P38 MAPK, JNK and Nuclear Factor-kappa B in Interleukin-1beta-induced Matrix Metalloproteinase-9 Expression in Rat Brain Astrocytes. J Neurochem. 2004;90(6):1477-88. PubMed PMID: 15341531.
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TY - JOUR T1 - Involvement of p42/p44 MAPK, p38 MAPK, JNK and nuclear factor-kappa B in interleukin-1beta-induced matrix metalloproteinase-9 expression in rat brain astrocytes. AU - Wu,Cheng-Ying, AU - Hsieh,Hsi-Lung, AU - Jou,Mei-Jie, AU - Yang,Chuen-Mao, PY - 2004/9/3/pubmed PY - 2004/10/28/medline PY - 2004/9/3/entrez SP - 1477 EP - 88 JF - Journal of neurochemistry JO - J. Neurochem. VL - 90 IS - 6 N2 - Matrix metalloproteinase (MMP)-9 expression induced by interleukin-1beta (IL-1beta) was investigated in rat brain astrocyte-1 (RBA-1). Here we report that the mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-kappaB) pathways participate in the induction of MMP-9 expression by IL-1beta. Zymographic, western blotting, and RT-PCR analyses showed that IL-1beta increased expression of MMP-9 mRNA and protein, which were inhibited by inhibitors of MEK1/2 (U0126), p38 (SB202190), and JNK (SP600125). In accordance with these findings, IL-1beta stimulated phosphorylation of p42/p44 MAPK, p38, and c-Jun N-terminal kinase (JNK), which was attenuated by U0126, SB202190, or SP600125, respectively. Furthermore, this up-regulation of MMP-9 mRNA and protein was blocked by a specific NF-kappaB inhibitor helenalin. Consistently, IL-1beta-stimulated translocation of NF-kappaB into the nucleus and degradation of inhibitory kappa B-alpha (IkappaB-alpha) was revealed by western blotting and immunofluorescence staining, which was blocked by helenalin, but not by U0126, SB202190, or SP600125. Taken together, these results suggest that in RBA-1 cells, activation of p42/p44 MAPK, p38, JNK and NF-kappaB pathways is essential for IL-1beta-induced MMP-9 gene expression via transcription and translation processes. An increased understanding of the signal transduction pathways involved in IL-1beta-induced MMP-9 expression on RBA-1 may be of potential therapeutic value in the treatment of inflammatory disease. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/15341531/Involvement_of_p42/p44_MAPK_p38_MAPK_JNK_and_nuclear_factor_kappa_B_in_interleukin_1beta_induced_matrix_metalloproteinase_9_expression_in_rat_brain_astrocytes_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=2004&volume=90&issue=6&spage=1477 DB - PRIME DP - Unbound Medicine ER -