Hypoxia-inducible factor 1 alpha (HIF1 alpha) is a transcriptional factor that plays a key role in the regulation of various molecules expressed in hypoxic conditions. Ischemic/hypoxic conditions are regarded as a distinct characteristic of dental pulp inflammation due to the encasement of pulp tissue within the rigid tooth structure. This study was performed to examine the role of HIF1 alpha in the regulation of interleukin (IL)-6, a proinflammatory cytokine expressed in inflamed dental pulp, in lipopolysaccharide (LPS)-stimulated human dental pulp cells (hDPCs). LPS stimulation promoted the expression of IL-6 in hDPCs, while HIF1 alpha suppressed the expression of IL-6. Moreover, HIFI a induced suppressor of cytokine signaling 3 (SOCS3) expression in LPS-stimulated hDPCs, and SOCS3 activity led to downregulate expression of CCAAT enhancer-binding protein beta (CEBP beta), an inducer of IL-6. LPS stimulation promoted HIFI a expression in hDPCs and mouse pulp tissue explants cultured under hypoxic conditions. These findings suggest that HIF1 alpha negatively regulates IL-6 synthesis in LPS-stimulated hDPCs via upregulation of SOCS3 and subsequent downregulation of CEBP beta. (C) 2019 Elsevier Inc. All rights reserved.