Hsp27 Regulates Pro-Inflammatory Mediator Release in Keratinocytes by Modulating NF-κB Signaling
- 1 May 2008
- journal article
- Published by Elsevier BV in Journal of Investigative Dermatology
- Vol. 128 (5), 1116-1122
- https://doi.org/10.1038/sj.jid.5701157
Abstract
Heat-shock protein 27 (Hsp27) is a member of the small Hsp family that functions as molecular chaperones and protects cells against environmental stress. Hsp27 is expressed in the upper epidermal layers of normal human skin and has been reported to play a role in keratinocyte differentiation and apoptosis. In this investigation, we show an additional role of Hsp27 in the regulation of inflammatory pathways in keratinocytes. Downregulation of Hsp27 using Hsp27-specific small interfering RNA increased prostaglandin E2 (PGE2) production in both unstimulated and tumor necrosis factor-α (TNF-α)-stimulated keratinocytes. Moreover, downregulation of Hsp27 increased the release of the pro-inflammatory cytokine IL-8 from TNF-α-stimulated and UV-irradiated keratinocytes, and this increase was inhibited by pretreatment with the NF-κB inhibitor BAY11-7082. Further studies showed that downregulation of Hsp27 resulted in induction of NF-κB reporter activity in keratinocytes. This correlated with enhanced degradation of IκB-α protein and accumulation of phosphorylated IκB-α in Hsp27 knockdown cells. Moreover, Hsp27 associated with the IκB kinase (IKK) complex. As synthesis of the pro-inflammatory cytokine IL-8 and the prostanoid PGE2 are regulated by NF-κB, this could be a probable mechanism by which Hsp27 modulates the production of these inflammatory cytokines. Thus, Hsp27 plays a protective role in regulating inflammatory responses in skin.Keywords
This publication has 43 references indexed in Scilit:
- Heat Shock Protein 27 Functions in Inflammatory Gene Expression and Transforming Growth Factor-β-activated Kinase-1 (TAK1)-mediated SignalingPublished by Elsevier BV ,2007
- Suppression of NF-κB Activation by Entamoeba histolytica in Intestinal Epithelial Cells Is Mediated by Heat Shock Protein 27Journal of Biological Chemistry, 2006
- Small interfering RNA knocks down heat shock factor-1 (HSF-1) and exacerbates pro-inflammatory activation of NF-κB and AP-1 in vascular smooth muscle cellsCardiovascular Research, 2006
- Role of p38 MAPK in UVB-Induced Inflammatory Responses in the Skin of SKH-1 Hairless MiceJournal of Investigative Dermatology, 2005
- HSP27 Is a Ubiquitin-Binding Protein Involved in I-κBα Proteasomal DegradationMolecular and Cellular Biology, 2003
- Human Keratinocytes Respond to Osmotic Stress by p38 Map Kinase Regulated Induction of HSP70 and HSP27Journal of Investigative Dermatology, 2001
- Detection of Differentially Regulated Genes in Keratinocytes by cDNA Array Hybridization: Hsp27 and Other Novel Players in Response to Artificial Ultraviolet RadiationJournal of Investigative Dermatology, 2001
- Ultraviolet B-Mediated Phosphorylation of the Small Heat Shock Protein HSP27 in Human KeratinocytesJournal of Investigative Dermatology, 2000
- Analysis of the Mechanism of Ultraviolet (UV) B Radiation – Induced Prostaglandin E2 Synthesis by Human Epidermoid Carcinoma CellsJournal of Investigative Dermatology, 1993
- Review: Transcriptional and post-transcriptional regulation of interleukin 1 gene expressionInternational Journal of Immunopharmacology, 1992