quiescent fibroblasts are more active in mounting robust inflammatory responses than proliferative fibroblasts静止的成纤维细胞更活跃在日益强劲比增生的成纤维细胞的炎症反应.pdfVIP

Quiescent Fibroblasts Are More Active in Mounting Robust Inflammatory Responses Than Proliferative Fibroblasts 1,2. 1. 1 1 1 Bo-Rui Chen , Huei-Hsuan Cheng , Wei-Chung Lin , Kai-Hsuan Wang , Jun-Yang Liou , Pei- Feng Chen1, Kenneth K. Wu1,2* 1 Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan, 2 Institute of Biotechnology, National Tsing Hua University, Hsin- Chu, Taiwan Abstract Quiescent cells are considered to be dormant. However, recent studies suggest that quiescent fibroblasts possess active metabolic profile and certain functional characteristics. We previously observed that serum-starved quiescent fibroblasts respond to proinflammatory stimuli by robust expression of cyclooxygenase-2 (COX-2), which declines after the quiescent fibroblasts are driven to proliferation. In this study, we elucidated the underlying signaling and transcriptional mechanism and identified by microarray genes with similar differential expression. By using pharmacological inhibitors coupled with gene silencing, we uncovered the key role of protein kinase C d (PKCd) and extracellular signal regulated protein kinase 1/2 (ERK1/2) signaling in mediating COX-2 expression in quiescent cells. Surprisingly, COX-2 expression in proliferative cells was not blocked by PKCd or ERK1/2 inhibitors due to intrinsic inhibition of PKCd and ERK1/2 in proliferative cells. Restrained COX-2 transcription in proliferative cells was attributable to reduced NF-kB binding. Microarray analysis identified 35 genes whose expressions were more robust in quiescent than in proliferative cells. A majority of those genes belong to proinflammatory cytokines, chemokines, adhesive molecu