芳香烃受体在人表皮、毛囊和皮脂腺上的表达及其意义北大核心CSCD

目的 观察芳香烃受体（AhR）在人表皮、毛囊及皮脂腺细胞上的表达及在二噁英作用下的激活情况。方法 采用免疫荧光和免疫组化法观察AhR蛋白在人面部表皮、毛囊、皮脂腺及体外培养的HaCaT细胞和SZ95人皮脂腺细胞上的表达情况;Western印记法观察2,3,7,8-四氯二苯-p-二噁英（TCDD）作用HaCaT细胞和SZ95细胞3 d后AhR蛋白表达的变化情况。结果 AhR蛋白在人面部皮肤表皮、毛囊、皮脂腺细胞上表达,并且AhR蛋白在表皮棘层和颗粒层的表达强于基底细胞层,在皮脂腺小叶的外周和中央表达强于皮脂腺小叶中间,在毛囊外毛根鞘和近毛小皮细胞上的表达强于内毛根鞘细胞。AhR蛋白在HaCaT细胞和SZ95细胞的细胞核和胞质中高表达。在TCDD作用下,HaCaT细胞和SZ95细胞内AhR蛋白表达明显下降,显示AhR在TCDD作用下被激活。结论 AhR在人表皮、毛囊、皮脂腺、HaCaT细胞及SZ95细胞上高表达,并在TCDD作用下激活,显示二噁英有可能通过AhR信号途径引起了人表皮、毛囊和皮脂腺的异常分化。     

四氯二苯并二恶英对SZ95人皮脂腺细胞细胞色素P4501A1表达的影响及其意义

【摘要】 目的 探讨环境污染物2,3,7,8-四氯二苯并二恶英（TCDD）影响人皮脂腺细胞的细胞色素P4501A1（CYP1A1）分子信号途径及氯痤疮的发生机制。方法 实时荧光PCR研究10 nmol/ L TCDD作用SZ95人皮脂腺细胞2 h后CYP1A1 mRNA表达的变化;细胞免疫组化和斑点印迹法研究10 nmol/L TCDD作用SZ95人皮脂腺细胞3 d后蛋白表达变化情况。结果 实时荧光 PCR研究显示,CYP1A1 mRNA在SZ95人皮脂腺细胞呈低量表达,在10 nmol/L TCDD作用下,CYP1A1 mRNA表达增强了5.622倍,差异有统计学意义（P < 0.05）。细胞免疫组化显示,CYP1A1蛋白在SZ95人皮脂腺细胞核及胞质中低量表达,在10 nmol/L TCDD作用下表达明显增强。斑点印迹法证实,10 nmol/L TCDD作用于SZ95人皮脂腺细胞3 d后CYP1A1蛋白相对定量值（4.233 ± 0.252）显著高于未加药的阴性对照组（0.123 ± 0.208）,差异有统计学意义（P < 0.05）。结论CYP1A1 mRNA和蛋白在SZ95人皮脂腺细胞上呈低量表达,但在TCDD作用下表达被激活,体外证明CYP1A1是TCDD影响人皮脂腺细胞异常分化的AhR下游靶位基因之一。 【关键词】 细胞色素P4501A1; 四氯二苯并二恶英; 皮脂腺; 细胞     

白藜芦醇对苯并芘诱导的人皮脂腺细胞炎症因子及相关基因表达的影响

【摘要】 目的 研究白藜芦醇对苯并芘诱导的SZ95人皮脂腺细胞炎症因子及相关基因表达的影响。方法 SZ95人皮脂腺细胞分为对照组、1 × 10-5 mol/L白藜芦醇组、1 × 10-5 mol/L苯并芘组及白藜芦醇 + 苯并芘组。实时荧光定量PCR检测各组SZ95人皮脂腺细胞中白细胞介素1α（IL-1α）、IL-6、芳香烃受体（AhR）、细胞色素酶P450（CYP）1A1、CYP1B1 mRNA表达;Western印迹检测各组p38丝裂原活化蛋白激酶（MAPK）磷酸化水平（磷酸化p38水平/p38水平）和AhR蛋白相对水平;酶联免疫吸附法检测各组细胞上清液中IL-1α、IL-6蛋白表达。多组间均数比较用单因素方差分析,组间两两比较采用LSD-t检验。结果 对照组、白藜芦醇组、苯并芘组及白藜芦醇 + 苯并芘组SZ95人皮脂腺细胞IL-1α的mRNA（2.045 ± 0.272、2.058 ± 0.154、3.124 ± 0.094、2.185 ± 0.337）和蛋白（9.132 ± 1.181、9.429 ± 0.771、20.361 ± 0.907、9.917 ± 0.897）表达水平差异均有统计学意义（F值分别为14.662、101.705,P值分别 < 0.01、 < 0.001）,其中白藜芦醇 + 苯并芘组IL-1α mRNA和蛋白相对水平低于苯并芘组（均P < 0.01）。此外,苯并芘组p38磷酸化水平显著高于对照组、白藜芦醇组及白藜芦醇 + 苯并芘组（F = 303.129,均P < 0.000 1）。白藜芦醇 + 苯并芘组AhR、CYP1A1和CYP1B1的mRNA表达较苯并芘组显著下调（t值分别为10.640、33.599、18.327,均P < 0.001）。苯并芘组细胞AhR蛋白表达低于白藜芦醇 + 苯并芘组（P < 0.001）。结论 白藜芦醇可抑制环境污染物苯并芘诱导的SZ95人皮脂腺细胞炎症因子IL-1α表达,该作用可能通过AhR和p38MAPK通路所介导。     

痤疮患者皮损处雄激素受体的表达

目的:研究雄激素受体(AR)在寻常性痤疮患者皮损处的表达.方法:用免疫组化法对15例男性寻常性痤疮患者的皮损及20例正常对照的皮肤组织进行了雄激素受体的检测.结果:寻常性痤疮患者皮损的表皮角质形成细胞、毛囊的外毛根鞘细胞、皮脂腺细胞、毛囊角栓部位的角质形成细胞及皮脂腺周围浸润的炎性细胞均有雄激素受体的表达,其表达水平明显高于正常对照组(P<0.05).结论:雄激素受体表达水平增高可能参与了痤疮的发病过程.     

成纤维细胞生长因子受体在人正常皮肤和伤口处的免疫定位

成纤维细胞生长因子(FGF)是一个有22个成员的细胞因子家族，与细胞表面受体结合调节细胞生长、增殖、分化和基质合成并参与炎症反应，其作用与细胞分化及生化状态和理化环境有关。目前发现有4种成纤维细胞生长因子受体(FGFR)，作者采用免疫组化技术检测了4种受体在正常皮肤和伤口处的表达。结果：①正常皮肤中FGFR的表达：FGFR-1表达于表皮各层、皮肤附属器、竖毛肌、血管和真皮成纤维细胞；FGFR-2在表皮、毛囊、皮脂腺、小汗腺、血管和成纤维细胞有表达，而且在基底层呈强阳性；FGFR-3在基底层的上部和毛囊内层呈强阳性；FGFR-4主要见于血管平滑肌、竖毛肌和小汗腺；②头皮生长期毛囊FGFR的表达：FGFR-1在毛发基质细胞、内外根鞘和毛乳头细胞强表达；FGFR-2的表达定位与FGFR-1相似，并且在毛囊根部基质细胞呈强阳性而角化区较弱；FGFR-3在毛球至峡部的内毛根鞘内段强表达，也见于外毛根鞘峡部和已分化的皮脂腺细胞及皮脂腺导管；FGFR-4仅见于毛囊周结缔组织鞘；③伤口处FGFR的表达：新生表皮基底层细胞FGFR-1和3呈强表达，而FGFR-2和4的表达较弱；基底层上部的细胞FG．FR-3强表达，而FGFR-1和2表达弱；肉芽和瘢痕组织中成纤维细胞／肌纤维母细胞表面FGFR-1和3的表达较强，而2和4呈弱阳性，而浸润单核细胞表面FGFR-1和3表达较强。讨论：正常表皮中4种FGFR表达的变化，提示在角质形成细胞分化过程中4种受体的表达发生着改变。研究表明，表皮细胞特异性表达FGFR-3亚型Ⅲb，而间质细胞同时表达FGFR-3的两个亚型Ⅲb和Ⅲc。其中Ⅲb与aFGF和FGF-9结合，而Ⅲc与aFGF和FGF-4高亲和力结合，与bFGF结合力弱而不与FGF-5结合。bFGF位于表皮基底层而aFGF则主要存在于棘层。aFGF和FGFR-3在基底层上部的正在分化的角质形成细胞中共表达，提示aFGF可能通过自分泌作用参与角质形成细胞的分化过程。Finch等发现基质细胞表达对人角质形成细胞有强促分裂作用的角质形成细胞生长因子，并发现其受体表达于正常人表皮基底层及银屑病表皮基底层和基底层上方的角质形成细胞。本研究发现，基底层中FGFR-2的表达，可能是角质形成细胞生长因子受体在表皮基底层和外毛根鞘的定位。Gonzalez等发现FGFR-1及其mRNA主要表达于表皮生发层，由此推测bFGF可能通过FGFR-1对基底细胞有促分裂作用，而aFGF则促进棘细胞的有丝分裂。动物实验表明：FGF和FGFR的表达与毛发的生长周期和发育有关。作者发现4种FGFR在正常人皮肤生长期毛囊的表达模式不同，特别在毛球根部毛母质细胞中FGFR-2的表达呈强阳性，结合动物实验结果，本研究提示真皮乳头FGF-2活化毛母质细胞表达FGFR-2并刺激毛母质细胞增生和毛发生长；毛囊内FGFR-1的表达，提示FGFR-1可能在角质形成细胞向毛发分化的终末过程中起一定的作用。FGFR-3在生长期毛囊中内外毛根鞘和皮脂腺的终末分化细胞中表达而在毛基质细胞内不表达，这可能是由于分化类型的差异，角质形成细胞表达不同的FGFR。     

血管生成素对人毛囊外毛根鞘角质形成细胞增殖的影响

目的:探讨血管生成素对体外培养的人毛囊外毛根鞘角质形成细胞增殖的影响.方法:采用两步酶消化法分离和培养人毛囊外毛根鞘角质形成细胞,将与绿色荧光蛋白基因共表达的血管生成素真核表达质粒pEGFP-ANG转染人毛囊外毛根鞘角质形成细胞,同时设立转染空质粒的pEGFP-C2组和只加转染液的阴性对照组,48 h后利用ELISA法检测细胞上清液中血管生成素的表达,同时四甲基偶氮唑蓝(MTT)法检测细胞增殖.另外,将不同浓度的重组人血管生成素(0～200μg/L)加入人毛囊外毛根鞘角质形成细胞中,培养48 h后MTT法检测细胞增殖,流式细胞仪检测细胞周期.结果:成功分离与培养了人毛囊外毛根鞘角质形成细胞,转染人血管生成素的细胞上清液中血管生成素的浓度明显高于转染pEGFP-C2组和阴性对照组(P＜0.001),且其能够明显促进人毛囊外毛根鞘角质形成细胞增殖(P＜0.001).另外,3.125～200.000 μg/L重组人血管生成素能够明显促进人毛囊外毛根鞘角质形成细胞增殖(P＜0.001),其中以12.500 μg/L浓度组作用最为显著.流式细胞仪检测结果表明12.500～200.000 μg/L重组人血管生成素能够显著增加细胞增殖指数(P<0.05).结论:内源性和外源性血管生成素均能明显促进体外培养的人毛囊外毛根鞘角质形成细胞增殖,提示血管生成素可能通过促进毛囊外毛根鞘角质形成细胞增殖而促进毛发生长.     

雌激素受体在女性面部皮肤的表达

用免疫组化方法检测雌激素受体在女性面部皮肤中的表达.探讨皮肤形态特点和老化与雌激素的关系.显示雌激素受体的两种亚型(ERα,ERβ)在皮肤均有表达,其中ERα只表达在皮脂腺细胞核中;ERβ在皮肤表达广泛,是皮肤的主要雌激素受体,真皮成纤维细胞、表皮基底细胞、皮脂腺细胞、毛囊外毛根鞘细胞、汗管内皮细胞均有ERβ表达.皮肤是雌激素重要的靶器官,可从各个方面影响皮肤的结构和功能.毛发的生长和脱落,皮脂分泌、皮肤老化进程都与雌激素有关.     

1,25二羟基维生素D3对毛囊外毛根鞘无色素黑素细胞激活的实验研究

目的研究1,25二羟基维生素D3(1,25-Dihydroxyvitamin D3,VID)对毛囊外毛根鞘无色素黑素细胞(amelanotic melanocytes,AMMC)的激活作用。方法以高、中、低3种不同浓度的1,25(OH)2D3作用于培养的人毛囊外毛根鞘AMMC,倒置显微镜观察细胞形态的变化,然后收集细胞,测定细胞酪氨酸酶活性和黑素含量,透射电镜观察药物作用前后AMMC内黑素小体的变化,最后通过Western blot方法半定量分析药物作用前后AMMC内酪氨酸酶(tyrosinase,TYR)、酪氨酸酶相关蛋白1(tyrosinase related protein-1,TRP-1)和酪氨酸酶相关蛋白2(tyrosinase relatedprotein-2,TRP-2)表达的变化。结果 VID能增加AMMC内酪氨酸酶活性,促进AMMC生成黑素,电镜结果显示药物作用后的AMMC内出现大量Ⅲ、Ⅳ期黑素小体。Western blot结果显示VID可以促进AMMC中TYR和TRP-1的表达,但对TRP-2的表达无明显影响。结论 VID通过促进黑素生成相关酶TYR和TRP-1的表达激活了AMMC。     

胸腺素β4影响毛囊生长的研究

目的:通过观察在不同浓度胸腺素β4干预下,毛囊外毛根鞘细胞的增殖以及毛发的生长情况,推测胸腺素β4促毛囊生长发育的作用机制.方法:取乳鼠触须部皮肤,分离毛囊及毛囊外毛根鞘细胞,加入不同浓度胸腺素β4,与空白组作对照,并用cell counting kit(CCK)-8细胞增殖曲线描述毛囊外毛根鞘细胞的增殖情况.结果:胸腺素β4干预组毛囊外毛根鞘细胞的增殖以及毛发的生长情况与对照组具有统计学差异,且浓度为0.015%胸腺素β4促进作用最明显.结论:胸腺素β4可通过促进毛囊外毛根鞘细胞的增殖来促进毛发生长.     

毛发疾病

941577 正常人体多毛部位皮肤雌激素受体的比较研究/周光平…//临床皮肤科杂志。-1994,23(2).-71～73 对10例毛发分布正常的健康男性头皮、眉部、胡须、腋部、阴部皮肤应用直接荧光组织化学法检测雌激素受体(ER)。结果:表皮细胞、毛囊外毛根鞘及少数内毛根鞘、皮脂腺、大小汗腺、立毛肌、真皮纤维母细胞、毛     

2,3,7,8-Tetrachlorodibenzo-p-dioxin alters sebaceous gland cell differentiation in vitro

Chloracne is a characteristic marker of intoxication by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or related compounds. Decreased lipogenesis is a prominent clinical sign in this disease. However, the activity of dioxins on human sebaceous glands is still unclear. In this study, the effects of TCDD on sebaceous gland differentiation were studied both in human skin samples maintained ex vivo and in cultured SZ95 sebocytes. Aryl hydrocarbon receptor (AhR) protein expression, the receptor for dioxin, was detected in SZ95 sebocytes. Its expression was markedly inhibited by TCDD. Furthermore, we detected a reduced release of neutral lipids (10(-10) -10(-8) M; P<0.001) and decreased expression of epithelial membrane antigen and keratin 7, all of which are specific markers of sebaceous differentiation. Markedly, increased expression of the keratinocyte differentiation marker keratin 10 and of peroxisome proliferators-activated receptor-δ was assessed in SZ95 sebocytes treated with TCDD. To corroborate these in vitro data, an ex vivo sebaceous gland-rich skin culture model was investigated. Obvious shrinkage of sebaceous glands with sebaceous duct hyperplasia and increased expression of keratin 10 in the atrophic sebaceous glands were observed on the 5th day of TCDD treatment. In conclusion, TCDD affects the differentiation of sebaceous gland cells probably by switching human sebaceous into keratinocyte-like differentiation. In addition and together with the results of a parallel study (J Dermatol Sci 58, 2010, 211), we provide evidence that TCDD effects on human sebocytes are mediated through the AhR signalling pathway.     

Expression patterns of programmed cell death 4 protein in normal human skin and some representative skin lesions

Expression of a tumor suppressor gene, programmed cell death 4 (PDCD4), was investigated at the protein level in the human skin. Immunohistochemically, PDCD4 protein expressed mainly in suprabasal layers, while PDCD4-positive and -negative areas were observed discontinuously in the basal cell layer of the epidermis. In hair follicles, the suprabulbar area including the hair and inner root sheath was immunoreactive, while the bulbar area, containing germinative cells which were strongly proliferating cell nuclear antigen (PCNA)-positive, was not or less. PDCD4 therefore appears to be important in the differentiation of hair follicles. PDCD4-positive cells were localized in the inside layers while PCNA-positive cells were located in the basal layer in the outer root sheath of hair follicles. The cells of sebaceous glands and sweat glands also were PDCD4-positive. The PDCD4 protein was localized mostly in nuclei of cutaneous cells. PDCD4 expression was found to be suppressed in the epidermis overlying an adult T-cell lymphoma (ATL), possibly reflecting a paracrine effect of factors produced by ATL cells. PDCD4 expression was suppressed in the keratinocyte cell line HaCaT by exposure of cultures to epidermal growth factor, transforming growth factor-beta1 or hepatocyte growth factor. Immunohistochemically, various skin cancers tended to show less PDCD4 expression than normal skin. Promotion of expression might prove useful in preventing or treating certain skin cancers.     

2,3,7,8-tetrachlorodibenzo-p-dioxin alters the differentiation of SZ95 sebocytes in vitro

Introduction:  Chloracne is an acneiform skin disease, which is considered to be the most specific and sensitive clinical condition of dioxin intoxication. Sebogenesis is decreased and skin xerosis is one of the most prominent clinical characteristics compared with acne vulgaris. However, the activity of dioxin on the sebaceous glands is still unclear. We studied the effects of 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD), which is a representative for a group of dioxins, on sebaceous lipid synthesis and expression of markers related to sebocyte differentiation in vitro .
Materials and Methods:  After pretreatment with and without linoleic acid (LA) 10⁻⁴  M for 3 days, SZ95 sebocytes were treated again with TCDD with and without linoleic acid 10⁻⁴  M for 3 additional days. Neutral lipids in SZ95 sebocytes were measured by the nile red microassay. Immunohistology and western blotting were used to detect expression of keratin 7 (a marker of undifferentiated sebocytes), EMA (a marker of differentiated sebocytes) and keratin 10 (a marker of keratinocyte differentiation).
Results:  The neutral lipid content of SZ95 sebocytes was markedly inhibited under treatment with TCDD in concentrations of 10⁻⁸  M , 10⁻⁹  M and 10⁻¹⁰  M ( P  < 0.001 respectively), in the presence of LA. SZ95 sebocyte lipid content was not affected by TCDD alone. Moreover, expression of keratin 7 and EMA decreased and keratin 10 increased under TCDD treatment.
Conclusions:  Dioxin affects sebaceous gland cell lipogenesis and differentiation in vitro , probably by switching the sebocyte into a kerationocyte lineage. These findings indicate that altered sebaceous gland differentiation is likely to be the major reason of decreased sebogenesis in patients with chloracne.     

Immunohistochemical evidence for differential distribution of 5α-reductase isoenzymes in human skin

Antibodies raised against fragments of synthetic peptides of human 5α-reductase isoenzymes 1 (h5αrl) and 2 (h5αr2) were applied to paraffin sections of human skin (scalp, eyelid, lip, breast, scrotum). Immunoreactive sites were differentially distributed, in that h5αrl immunoreactivity was present in the nuclei of cells in the stratum germinativum (basal and lower portion of the spinous layer) of the epidermis, subepithelial tibroblasts, adipocytes, smooth muscle cells of the scrotal tunica dartos, basal cells of sebaceous glands, excretory duct cells of sweat glands, cells of the dermal papilla and fibrous and outer epithelial sheath of hair roots, as well as endothelial cells of small vessels and Schwann cells of cutaneous myelinated nerves. In contrast, immunoreactivity for h5αr2 was found in the cytoplasm of the cells of the spinous layer (and far less intensely in the basal layer) of the epidermis, subepidermal fibrocytes, and especially in subcutaneous adipocytes. Immunoreactivity was strongest in the non-keratinized portion of the inner epithelial sheath and the cuticle of hair follicles, whereas other portions of the hair root were negative. Sweat glands were stained, whereas sebaceous glands showed only weak diffuse immunoreactivily. In mucoculaneous zones, salivary glands and conjunctival epithelium showed immunoreactive cells. Vascular endothelium displayed immunoreactivity only in the genital region. We present experimental evidence for a differential distribution of 5α-reductase isoenzymes in human skin. This might reflect a diversity in the response of different areas of the skin to androgenic challenge.     

Cutaneous androgen metabolism: basic research and clinical perspectives

The skin, especially the pilosebaceous unit composed of sebaceous glands and hair follicles, can synthesize androgens de novo from cholesterol or by locally converting circulating weaker androgens to more potent ones. As in other classical steroidogenic organs, the same six major enzyme systems are involved in cutaneous androgen metabolism, namely steroid sulfatase, 3beta-hydroxy-steroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, steroid 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase, and aromatase. Steroid sulfatase, together with P450 side chain cleavage enzyme and P450 17-hydroxylase, was found to reside in the cytoplasm of sebocytes and keratinocytes. Strong steroid sulfatase immunoreactivity was observed in the lesional skin but not in unaffected skin of acne patients. 3beta-hydroxysteroid dehydrogenase has been mainly immunolocalized to sebaceous glands, with the type 1 being the key cutaneous isoenzyme. The type 2 17beta-hydroxysteroid dehydrogenase isoenzyme predominates in sebaceous glands and exhibits greater reductive activity in glands from facial areas compared with acne nonprone areas. In hair follicles, 17beta-hydroxysteroid dehydrogenase was identified mainly in outer root sheath cells. The type 1 5alpha-reductase mainly occurs in the sebaceous glands, whereby the type II isoenzyme seems to be localized in the hair follicles. 3alpha-hydroxysteroid dehydrogenase converts dihydrotestosterone to 3alpha-androstanediol, and the use of 3alpha-androstanediol glucuronide serum level to reflect the hyperandrogenic state in hirsute women may be a reliable parameter, especially for idiopathic hirsutism. In acne patients it is still controversial if 3alpha-androstanediol glucuronide or androsterone glucuronide could serve as suitable serum markers for measuring androgenicity. Aromatase, localized to sebaceous glands and to both outer as well as inner root sheath cells of anagen terminal hair follicles, may play a "detoxifying" role by removing excess androgens. Pharmacologic development of more potent specific isoenzyme antagonists may lead to better clinical treatment or even prevention of androgen-dependent dermatoses.     

Expression of androgen receptors in skin appendage tumors: An immunohistochemical study

Androgen receptor (AR) expression was examined in normal skin and in 52 cases of various skin appendage tumors using a monoclonal antibody (F39.4.1) raised against the N-terminal domain of human AR. Microwave oven heating in citrate buffer solution followed by immunostaining with the labeled streptavidin biotin (LSAB) method was applied to formalin-fixed paraffin-embedded sections. Immunoreactive AR was restricted to the nuclei. In normal skin, AR was consistently localized in seboblasts and in some differentiated sebocytes, and variable expression was seen in luminal epithelial cells of eccrine and apocrine glands in the secretory portion. Hair follicles and epidermis showed no reactivity. In sweat gland tumors, AR was identified locally in inner layer cells of the tubuloglandular component of ten of thirteen chondroid syringomas but the remaining tumors were nonreactive. In sebaceous gland tumors, benign tumors with mature sebaceous elements (sebaceous nevi and sebaceous adenomas) showed AR expression, but the sebaceous epitheliomas and sebaceous carcinomas lost their expression. No AR expression was observed in hair follicle tumors, except in AR-positive mature sebaceous glands incorporated into the cyst wall of steatocystomas.     

Doxorubicin-induced alopecia is associated with sebaceous gland degeneration

Alopecia, accompanied by skin dryness, is one of the distressing side effects often occurring in chemotherapy-treated cancer patients. Little is known of the effects of chemotherapy on sebaceous glands, despite their importance in hair follicle homeostasis. This study investigates sebaceous gland morphology and the response of SZ95 sebaceous gland cell line to doxorubicin (DXR) treatment. The morphology of sebaceous glands during intraperitoneal DXR treatment was investigated by optical and electron microscopy in a 7-day-old rat model and further confirmed in an adult mouse model. Moreover, in vitro studies using the SZ95 sebaceous gland cell line were performed to assess the response of sebocytes to DXR in terms of cell proliferation, apoptosis, and necrosis. DXR treatment induced sebaceous gland regression and occasionally caused their complete disappearance. This observed damage and disappearance preceded DXR-induced hair loss. In vitro experiments using the SZ95 sebaceous gland cell line indicated that DXR treatment induced a differentiation process leading to premature sebocytes apoptosis. Owing to the importance of the sebaceous gland in hair follicle homeostasis, DXR-induced involution of this gland might be related to subsequent hair loss.     

Expression and localization of Artemis serine 516 phosphorylation in human scalp skin

Artemis phosphorylation at serine 516 (Ser516) has important regulatory functions in the repair of radiation‐induced DNA damage, V(D)J recombination, p53‐dependent apoptosis and cell cycle control. Accordingly, Artemis mutations can lead to Omenn syndrome, which is associated with human radiosensitive severe combined immunodeficiency syndrome and alopecia. In this study, we investigated the expression of Ser516 phosphorylation of Artemis in the epidermis and epidermal appendages in normal human scalp skin. Immunofluorescence analysis revealed Ser516 phosphorylation of Artemis in the upper and middle portion of anagen hair follicle [including outer root sheath (ORS), inner root sheath but not stratum basale], hair matrix, sebaceous glands (secretory and ductal portions), eccrine sweat glands (secretory and ductal portions) and epidermis (stratum basale and stratum granulosum), respectively. Artemis phosphorylation at Ser516 was most prominent in ORS keratinocytes. Therefore, we suggest that phosphorylation of Artemis at Ser516 could be involved in regulation of human epidermal appendages.