Background: Acne is a common disorder of the human pilosebaceous unit, yet the mechanisms underlying\r\nhyperkeratinisation and subsequent inflammation (comedogenesis) remain to be determined, although cutaneous\r\npathogens are implicated. Previously, it was reported that the release of the cytokine interleukin-1a (IL-1a) by\r\nkeratinocytes of the sebaceous duct was pivotal in the life cycle of the comedone, mediating both its development\r\nand its spontaneous resolution. Toll-like receptors are a family of molecules that recognise pathogen associated\r\nmolecular patterns (PAMPs) presented by microorganisms, initiating a signalling cascade terminating in the release\r\nof antimicrobial compounds and cytokines.\r\nMethods: We used ex vivo sebaceous gland and primary monolayer keratinocyte culture, alongside ELISAs,\r\nimmunohistochemistry, Western blotting and RT-PCR to investigate the contribution of TLR activation to\r\nacne pathogenesis.\r\nResults: We found TLR2 to be expressed in basal and infundibular keratinocytes, and sebaceous glands, and its\r\nactivation provoked the release of IL-1a from primary human keratinocytes in vitro. The exposure of\r\nmicrodissected human sebaceous glands to PAMPs specific for TLR2 in vitro resulted in a pattern of IL-1a like\r\ncornification after seven days of exposure.\r\nConclusions: TLR activation and secretion of IL-1a from keratinocytes may be initiating steps in comedogenesis\r\nand, therefore, critical to the pathophysiology of acne.
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