Interleukin-1 stimulates cytokines, prostaglandin E2 and matrix metalloproteinase-1 production via activation of MAPK/AP-1 and NF-κB in human gingival fibroblasts
Interleukin-1 stimulates cytokines, prostaglandin E2 and matrix metalloproteinase-1 production via activation of MAPK/AP-1 and NF-κB in human gingival fibroblasts
复制标题
DOI：
10.1016/j.cyto.2004.10.009
复制
发表时间：
2005-02-21
期刊：
影响因子：
3.8
通讯作者：
Hasegawa, K
中科院分区：
文献类型：
--
作者：
Kida, Y;Kobayashi, M;Hasegawa, K
白介素1(IL-1)刺激包括成纤维细胞在内的宿主细胞产生多种炎症介质和分解代谢因子，在慢性炎症性疾病(如牙周病)组织破坏的免疫病理反应中发挥重要作用。我们全面研究了丝裂原活化蛋白激酶(MAPKs)/激活蛋白-1(AP-1)和IkappaB激酶(IKKS)/IkappaB/核因子-kappaB(NF-kappaB)在IL-1β刺激的人牙龈成纤维细胞(HGF)产生IL-6、IL-8、前列腺素E-2(PGE(2))和基质金属蛋白酶-1(MMP-1)中的作用。IL-1β同时激活的三种MAPK，细胞外信号调节蛋白(ERK)、p38MAPK和c-jun氨基末端蛋白(JNK)，不同程度地介导了AP-1的c-fos和c-jun基因的表达和DNA结合。1KKalpha/β/IkappaB-α/NF-kappaB也参与了IL-1信号转导通路。此外，IL-1β通过激活3个MAPK和NF-kappaB刺激HGF产生IL-6、IL-8、PGE(2)和MMP-1，作为每种MAPK和NF-kappaB的抑制剂显著抑制IL-1β刺激因子的产生，尽管这些途径在IL-1β的活性中也可能起着不同的作用。我们的结果有力地表明，MAPKs/AP-1和IKK/IkappaB/NF-kappaB级联信号通路协同介导IL-1β刺激HGF合成IL-6、IL-8、PGE(2)和MMP-1。(C)2004 E Sevier Ltd。保留所有权利。
Interleukin-1 (IL-1) plays a crucial role in the immunopathological responses involved with tissue destruction in chronic inflammatory diseases, such as periodontal disease, as it stimulates host cells including fibroblasts to produce various inflammatory mediators and catabolic factors. We comprehensively investigated the involvement of mitogen-activated protein kinases (MAPKs)/ activator protein-1 (AP-1) and IkappaB kinases (IKKS)/IkappaBs/nuclear factor-kappaB (NF-kappaB) in IL-1beta-stimulated IL-6, IL-8, prostaglandin E-2 (PGE(2)) and matrix metalloproteinase-1 (MMP-1) production by human gingival fibroblasts (HGF). Three MAPKs, extracellular signal-regalated kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK), which were simultaneously activated by IL-1beta, mediated subsequent c-fos and c-jun mRNA expression and DNA binding of AP-1 at different magnitudes. lKKalpha/beta/IkappaB-alpha/NF-kappaB was also involved in the IL-1 signaling cascade. Further, IL-1beta stimulated HGF to produce IL-6, IL-8, PGE(2) and MMP-1 via activation of the 3 MAPKs and NF-kappaB, as inhibitors of each MAPK and NF-kappaB significantly suppressed the production of IL-1beta-stimulated factors, though these pathways might also play distinct roles in IL-1beta activities. Our results strongly suggest that the MAPKs/AP-1 and IKK/IkappaB/NF-kappaB cascades cooperatively mediate the IL-1beta-stimulated synthesis of IL-6, IL-8, PGE(2) and MMP-1 in HGF. (C) 2004 E sevier Ltd. All rights reserved.