BackgroundAcne is a common disorder of the human pilosebaceous unit, yet the mechanisms underlying hyperkeratinisation and subsequent inflammation (comedogenesis) remain to be determined, although cutaneous pathogens are implicated. Previously, it was reported that the release of the cytokine interleukin-1α (IL-1α) by keratinocytes of the sebaceous duct was pivotal in the life cycle of the comedone, mediating both its development and its spontaneous resolution. Toll-like receptors are a family of molecules that recognise pathogen associated molecular patterns (PAMPs) presented by microorganisms, initiating a signalling cascade terminating in the release of antimicrobial compounds and cytokines.MethodsWe used ex vivo sebaceous gland and primary monolayer keratinocyte culture, alongside ELISAs, immunohistochemistry, Western blotting and RT-PCR to investigate the contribution of TLR activation to acne pathogenesis.ResultsWe found TLR2 to be expressed in basal and infundibular keratinocytes, and sebaceous glands, and its activation provoked the release of IL-1α from primary human keratinocytes in vitro. The exposure of microdissected human sebaceous glands to PAMPs specific for TLR2 in vitro resulted in a pattern of IL-1α like cornification after seven days of exposure.ConclusionsTLR activation and secretion of IL-1α from keratinocytes may be initiating steps in comedogenesis and, therefore, critical to the pathophysiology of acne.
Follicular ageing is characterized by transcriptional changes associated with diverse aspects of keratinocyte metabolism, proliferation and development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.