¹Preclinical Pharmacology, Johnson and Johnson Skin Research Center, CPPW, a Unit of Johnson & Johnson Consumer Companies Inc., Skillman, New Jersey, USA

Correspondence: Dr Michael D. Southall, Preclinical Pharmacology, Johnson & Johnson, 199 Grandview Road, Skillman, New Jersey 08558, USA. E-mail: msoutha@cpcus.jnj.com

Received 8 August 2007; Revised 17 September 2007; Accepted 27 September 2007; Published online 15 November 2007.

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- (TNF-)-stimulated keratinocytes. Moreover, downregulation of Hsp27 increased the release of the pro-inflammatory cytokine IL-8 from TNF--stimulated and UV-irradiated keratinocytes, and this increase was inhibited by pretreatment with the NF-B inhibitor BAY11-7082. Further studies showed that downregulation of Hsp27 resulted in induction of NF-B reporter activity in keratinocytes. This correlated with enhanced degradation of IB- protein and accumulation of phosphorylated IB- in Hsp27 knockdown cells. Moreover, Hsp27 associated with the IB kinase (IKK) complex. As synthesis of the pro-inflammatory cytokine IL-8 and the prostanoid PGE₂ are regulated by NF-B, 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.