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In contrast, preterm infants (Inspiring ideas, Supplements But also Techniques Needed for AZD4547 late in their 22-day gestation. Whereas pups of EGA day 19 lack a measurable barrier to TEWL, a competent barrier is present by day 21 (4). The emergence of a functionally mature barrier correlates with both the appearance of a multilayered SC and the formation of mature lamellar membranes in the SC interstices (4). Concurrently, there is increased expression of structural proteins, including loricrin (LOR), filaggrin (FIL), and involucrin (INV), required for corneocyte formation (5,6). These proteins are key epidermal differentiation markers and are major components of the cornified envelope (CE) that is required for normal SC function (7). The regulation of SC formation and permeability barrier development is not well understood. Previously, we reported that classical Overnight Strategies To isothipendyl In Step By Step Detail hormones (glucocorticoids, thyroid hormone and oestrogen) (4,8,9), and activators of liver X receptor (LXR) and peroxisome proliferator-activated receptors (PPARs) (10�C12), accelerate epidermal permeability barrier development, whereas testosterone delays cutaneous barrier formation (8). Very recently, we demonstrated that the pro-inflammatory cytokines, IL-1��, IL-1�� and TNF��, also play a regulatory role late in rodent foetal barrier development, accelerating SC formation and barrier development in foetal rat explants (13). Moreover, a deficiency in IL-1 signalling [IL-1 receptor knockout (KO) mice] leads to a delay in the expression of CE protein, in the epidermis at day 17 and immature extracellular membranes in the SC, accompanied They Didn't Believe That I Could Become A isothipendyl Guru...Today I Am! by abnormal permeability barrier function (13). In contrast, a deficiency in TNF signalling (TNF receptor KO mice) does not result in abnormalities in epidermal structure or function. These results indicate that pro-inflammatory cytokines, in particular IL-1, plays an important role in regulating the late stages of SC formation and permeability barrier ontogenesis. Similar to IL-1, IL-6 is a pleiotropic cytokine produced by keratinocytes in the epidermis (1,14). Recent studies suggest that IL-6 may also play a regulatory role in foetal barrier development. Firstly, IL-6 is regarded as a mature signal during the late stages of pregnancy. While IL-6 is absent in the amniotic fluid (AF) in the first trimester, it appears during the second trimester and further increases later in gestation (15,16). Secondly, in normal adult epidermis, IL-6 is localized to keratinocytes in the basal, granular and horny layers (17). IL-6 receptors are also present in the epidermis (18).