Dihydrotestosterone-Inducible IL-6 Inhibits Elongation of Human Hair Shafts by Suppressing Matrix Cell Proliferation and Promotes Regression of Hair Follicles in Mice

Autocrine and paracrine factors are produced by balding dermal papilla (DP) cells following dihydrotestosterone (DHT)-driven alterations and are believed to be key factors involved in male pattern baldness. Herein we report that the IL-6 is upregulated in balding DP cells compared with non-balding DP cells. IL-6 was upregulated 3hours after 10–100nM DHT treatment, and ELISA showed that IL-6 was secreted from balding DP cells in response to DHT. IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) were expressed in follicular keratinocytes, including matrix cells. Recombinant human IL-6 (rhIL-6) inhibited hair shaft elongation and suppressed proliferation of matrix cells in cultured human hair follicles. Moreover, rhIL-6 injection into the hypodermis of mice during anagen caused premature onset of catagen. Taken together, our data strongly suggest that DHT-inducible IL-6 inhibits hair growth as a paracrine mediator from the DP

Preventative Effects of Antioxidants against PM10 on Serum IgE Concentration, Mast Cell Counts, Inflammatory Cytokines, and Keratinocyte Differentiation Markers in DNCB-Induced Atopic Dermatitis Mouse Model

Particulate matter (PM) can cause oxidative stress, inflammation, and skin aging. We investigated the effects of antioxidants such as dieckol, punicalagin, epigallocatechin gallate (EGCG), resveratrol, and Siegesbeckiae Herba extract (SHE) against PM < 10 μm (PM10) on serum IgE concentration, mast cell counts, inflammatory cytokines, and keratinocyte differentiation markers in a 2,4-Dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. Seven-week-old BALB/c mice were sensitized with 2% DNCB. Atopic dermatitis-like lesions were induced on the mice with 0.2% DNCB. Antioxidants and PM10 were applied to the mice for 4 weeks. PM10 increased the serum IgE concentration and spleen weight in mice, and all antioxidants downregulated these parameters. Histological examination showed an increase in epidermal thickness and mast cell counts in response to PM10, and all antioxidants showed a decrease. PM10 upregulates the expression of inflammatory cytokines, including interleukin (IL)-1β, IL-4, IL-6, IL-17α, IL-25, IL-31 and thymic stromal lymphopoietin (TSLP) in mice, and all antioxidants inhibited the upregulation of inflammatory cytokines. ELISA showed the same results as real-time PCR. PM10 downregulates the expression of keratinocyte differentiation markers, including loricrin and filaggrin, in mouse keratinocytes and antioxidants prevented the downregulation of the keratinocyte differentiation markers. Conclusively, PM10 aggravated the DNCB-induced mouse model in serum IgE concentration, mast cell counts, inflammatory cytokine, and keratinocyte differentiation markers. In addition, antioxidants modulated changes in the DNCB-induced mouse model caused by PM10

Schematic diagram of experiments and the selection of SNPs in human <i>RAD51</i> and <i>RAD52</i> genes.

<p>(A) Diagram indicating the method of SNP selection. The SNPs in <i>hRAD51</i> and <i>hRAD52</i> were selected using the National Center for Biotechnology Information Single Nucleotide Polymorphism Database (NCBI dbSNP), (<a href="http://www.ncbi.nlm.nih.gov/snp/" target="_blank">http://www.ncbi.nlm.nih.gov/snp/</a>). (B) Missense SNPs located in functional domains were compared with genetic variations using SIFT and PolyPhen. “Deleterious” and “Probably damaging” allelic mutants might affect function via structural alterations of Rad51 and Rad52. (C) Comparison of the functional domains of Rad51 in humans and yeast [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124152#pone.0124152.ref030" target="_blank">30</a>]. * regions containing <i>rad51-F317I</i> and <i>rad51-K371Q</i> mutations. (D) Comparison of the functional domains of Rad52 in humans and yeast [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124152#pone.0124152.ref031" target="_blank">31</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124152#pone.0124152.ref032" target="_blank">32</a>]. * regions containing <i>rad52-G41R</i>, <i>rad52-R52W</i>, and <i>rad52-G107C</i> mutations.</p

Protein structures of human wild-type proteins and the Rad51 and Rad52 variants.

<p>(A) Protein structures predicted by SWISS-MODEL were visualized by PyMOL. The wild type is represented in the left panel colored in green. The center panel shows the variants colored in aqua, and the right panel shows a merged structure. Variation sites were mapped by the full structure of amino acid side chains. Atoms of the side chains at the variation sites were coded by color (blue for nitrogen, red for oxygen, and yellow for sulfur). (B) Average Calpha RMSD of 10-amino acid fragments of variants of Rad51 and Rad52. Average RMSDs of 10 consecutive Calpha were plotted against their position. AUCs of RMSD were calculated by summation of the RMSD x 10. AUCpeaks (AUC of peaks) containing mutation sites were marked on the top of the peaks.</p

Spore viability of Rad51 and Rad52 variants.

<p>Analysis of meiotic spore viability in parallel cultures for WT, <i>rad51</i>, and <i>rad52</i> mutant strains. Cells were cultured in SPM (1% potassium acetate and 0.02% raffinose) for 18 h to induce sporulation. Approximately 100 tetrads were dissected for each strain.</p