No abstract

To understand better the mechanisms by which thyroid hormone can exert its effects on the hair follicle, we looked for the expression of members of the thyroid hormone receptor (TR) family in human hair follicles. Immunoreactive TRs were detected in both dermal and epithelial compartments of the human pilosebaceous unit. Using reverse transcriptase-polymerase chain reaction, we established that TRbeta1 was the predominant form of TR expressed in the human hair follicle. In addition, we investigated the effects of 3,3', 5-triiodo-L-thyronine (T3) on the survival of human hair follicles in vitro, to understand the role of this thyroid hormone on hair follicle homeostasis. A physiological level of free T3 significantly enhanced human hair survival in vitro.

Using reverse transcriptase polymerase chain reaction we showed that freshly plucked human anagen hair expressed both type 1 (80 kD) and type 2 (60 kD) interleukin (IL)-1 receptor mRNAs. The IL-1 receptor type 1 was functional since after in vitro stimulation of plucked hair with IL-1Α, we observed the induction of mRNA(s) for the inflammatory cytokines IL-1Β, tumour necrosis factor Α and IL-6 as well as for the chemokines monocyte chemotactic and activating factor and IL-8. In addition, the growth of dissected human anagen hairs in culture in vitro was significantly and dose-depen-dently inhibited by IL-1Α as a consequence of hair bulb degradation. These observations, together with those of other authors in IL-1Α transgenic mice evidence the inhibitory role of IL-1 on human hair growth. Therefore, in order to identify individuals with high inflammatory potential in their hair follicle environment, we designed a rapid and simple assay to detect variations in the level of IL-1Α production in the overnight supernatant of plucked hairs in culture. We observed that 32.7% of the specimens from the volunteers tested (n = 116) could be considered highly inflammatory in terms of IL-1Α production. Altogether, these results suggest that in alopecia androgenetica, hair growth might be negatively influenced by IL-1, directly produced by the outer root sheath keratinocytes. Consequently, identifying the ‘inflammatory alopecic individual’ might be of clinical interest to discriminate among individuals for whom anti-IL-1 strategies might be of therapeutic relevance.

Data from the literature indicate that nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, naproxen, piroxicam, or ibuprofen, induce hair loss in vivo. These NSAIDs are well-known inhibitors of both the cytoprotective isoform of prostaglandin endoperoxide synthase-1 (PGHS-1) and of the inducible form (PGHS-2). By immunohistochemical staining, we found that PGHS-1 is the main isoform present in the dermal papilla from normal human hair follicle (either anagen or catagen), whereas PGHS-2 was only faintly and exclusively expressed in anagen dermal papilla. Thus, PGHS-1 might be the primary target of the hair growth-inhibitory effects of NSAIDs. We thus speculated that activation of PGHS-1 might be a mechanism by which minoxidil (2,4-diamino-6-piperidinopyrimidine-3-oxyde) stimulates hair growth in vivo. We demonstrate here that minoxidil is a potent activator of purified PGHS-1 (AC50 = 80 microM), as assayed by oxygen consumption and PGE2 production. This activation was also evidenced by increased PGE2 production by BALB/c 3T3 fibroblasts and by human dermal papilla fibroblasts in culture. Our findings suggest that minoxidil and its derivatives may have a cytoprotective activity in vivo and that more potent second-generation hair growth-promoting drugs might be designed, based on this mechanism.

Vitreoscilla filiformis (Vf), a filamentous bacteria living in fresh water is thought to contribute to the observed beneficial effects of Spa water on skin. An active fraction obtained from a Vf biomass was evaluated for its ability to modulate mRNA expression in cultured skin cells. cDNA array analysis was conducted first using a customized membrane including 1176 selected and fully identified genes involved in skin physiology and homeostasis then the newly developed full genome U133 plus 2.0 GeneChip from Affymetrix. The mitochondrial protective manganese superoxide dismutase (MnSOD/SOD-2) was identified as a preferentially induced mRNA target in both normal human dermal fibroblasts and keratinocytes. Induction at the transcriptional level in both cell types was confirmed using quantitative real time/polymerase chain reaction and a kinetic analysis revealed a maximal increase in mRNA expression 20 h after stimulation with Vf extract (Vfe). Using immunofluorescent (fluorescent cell sorter) analysis, an induction of MnSOD protein in both normal human dermal skin fibroblasts (x1.6; P < 0.01) and epidermal keratinocytes (x1.4; P < 0.01) was confirmed. As MnSOD is a major inducible free-radical scavenger in skin, these results suggest that the Vfe could induce skin cells to produce their own endogenous protective defences in vivo against both exogenous environmental stressors such as UV irradiation or microflora as well as to combat endogenous sources of deleterious free radicals involved in skin ageing. Finally, in order to confirm the in vivo potential of this original extract in human, we evaluated its protective activity vs. placebo on the generation of sunburn cells in epidermis under UVB stress. As expected from in vitro profiling, Vfe was indeed found to significantly inhibit the appearance of sunburn cells in UVB-exposed areas, a signature of skin alteration which has been suggested to be linked to a defect in MnSOD protective activity. Altogether, those data suggest that the combination of a suitable protective UV filter together with this bioactive Vfe might improve skin protection through complementary pathways.