Wen-Teng Chang1, Ming-Yuan Hong2, Chien-Liang Chen3, Chi-Yuan Hwang2, Cheng-Chieh Tsai4, Chia-Chang Chuang5. 1. Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, 701, Taiwan. 2. Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 3. Department of Physical Therapy, I-Shou University, Kaohsiung, Taiwan. 4. Department of Nursing, Chung Hwa University of Medical Technology, Tainan, 701, Taiwan. 5. Department of Emergency Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. chuanger@mail.ncku.edu.tw.
Abstract
BACKGROUND: Glucocorticoids (GCs) have been extensively used as essential modulators in clinical infectious and inflammatory diseases. The GC receptor (GR) is a transcription factor belonging to the nuclear receptor family that regulates anti-inflammatory processes and releases pro-inflammatory cytokines, such as interleukin (IL)-6. RESULTS: Five putative GR binding sites and other transcriptional factor binding sites were identified on theIL-6 promoter, and dexamethasone (DEX) was noted to reduce the lipopolysaccharide (LPS)-induced IL-6 production. Among mutant transcriptional factor binding sites, nuclear factor-kappa B (NF-κB), activator protein (AP)-1, and specificity protein (Sp)1-2 sites reduced basal and LPS-induced IL-6 promoter activities through various responses. The second GR binding site (GR2) was noted to play a crucial role in both basal and inducible promoter activities in LPS-induced inflammation. CONCLUSIONS: We concluded that selective GR2 modulator might exert agonistic and antagonistic effects and could activate crucial signaling pathways during the LPS-stimulated inflammatory process.
BACKGROUND: Glucocorticoids (GCs) have been extensively used as essential modulators in clinical infectious and inflammatory diseases. The GC receptor (GR) is a transcription factor belonging to the nuclear receptor family that regulates anti-inflammatory processes and releases pro-inflammatory cytokines, such as interleukin (IL)-6. RESULTS: Five putative GR binding sites and other transcriptional factor binding sites were identified on theIL-6 promoter, and dexamethasone (DEX) was noted to reduce the lipopolysaccharide (LPS)-induced IL-6 production. Among mutant transcriptional factor binding sites, nuclear factor-kappa B (NF-κB), activator protein (AP)-1, and specificity protein (Sp)1-2 sites reduced basal and LPS-induced IL-6 promoter activities through various responses. The second GR binding site (GR2) was noted to play a crucial role in both basal and inducible promoter activities in LPS-induced inflammation. CONCLUSIONS: We concluded that selective GR2 modulator might exert agonistic and antagonistic effects and could activate crucial signaling pathways during the LPS-stimulated inflammatory process.
Authors: Ilse M E Beck; Wim Vanden Berghe; Linda Vermeulen; Keith R Yamamoto; Guy Haegeman; Karolien De Bosscher Journal: Endocr Rev Date: 2009-11-04 Impact factor: 19.871
Authors: Rajeshwari H Patil; M Naveen Kumar; K M Kiran Kumar; Rashmi Nagesh; K Kavya; R L Babu; Govindarajan T Ramesh; S Chidananda Sharma Journal: Gene Date: 2017-12-14 Impact factor: 3.688