痤疮易感基因的研究进展

痤疮是发生于毛囊皮脂腺的一种慢性炎症性疾病,发病机制尚不完全清楚.目前认为,主要与雄激素、皮脂分泌增多、毛囊导管的异常角化、痤疮丙酸杆菌感染、外界因素、机体的免疫反应和遗传有关.近年来研究表明,痤疮是一种多基因遗传病,尤其是重型痤疮与遗传密切相关.CYP11α、CYP17、CYP1A1、雄激素受体基因、CYP21等基因被认为是痤疮易感基因.因此,探讨痤疮的易感基因,对痤疮尤其是重型痤疮的早期诊断、治疗和预防具有重要意义.

Abstract：

Acne is a common chronic inflammatory disease affecting hair follicles and sebaceous glands with unclear pathogenesis. It is a multifactorial disease and several pathogenetic factors have been identified, including the increase of androgen and sebum excretion, follicular hyperkeratinization, infection with Propionibacterium acnes, external factors, innate immunity, genetics, etc. Latest studies have indicated that acne is a polygenic disease and there is a particularly close correlation between severe acne and heredity. Many predisposing genes have been discovered for acne, including human CYP11α gene, CYP17 gene, CYP1A1gene, androgen receptor gene, CYP21 gene, etc. Therefore, the investigation into susceptible genes for acne may be beneficial to the early diagnosis, treatment and prevention of severe acne.     

痤疮的发病机制及其治疗

重度痤疮以显著的炎症反应、反复发作及易留下永久性瘢痕为特点,仍是当今痤疮治疗的一个难题.重度痤疮的发病有一定的人群倾向性,它与个体的炎症及免疫反应、遗传因素、性激素水平、氧化应激反应及血清生化等相关,治疗主要为药物治疗及物理治疗,其中对痤疮瘢痕的治疗也是重度痤疮治疗中很重要的一部分.研究重度痤疮的发病机制可在一定程度上预防痤疮发展为重度痤疮,并且指导临床治疗.

Abstract：

Severe acne is characterized by evident inflammatory reaction, recrudescence and inclination to leave permanent scars.Its treatment is still a troublesome problem over the world.The development of severe acne has a certain tendency in populations, and is related to the inflammatory and immune responses, genetic factors, sexual hormone levels, oxidative stress and serum biochemistry in individuals.Severe acne is mainly managed by medication and physical therapy.The treatment of acne scar is an important part of severe acne management.So, to study the pathogenesis of severe acne may benefit the prevention and control of it.     

痤疮丙酸杆菌的新命名及其与寻常痤疮的相关性

【摘要】 近来,有研究者建议将痤疮丙酸杆菌命名为Cutibacterium acnes（C. acnes）,以更好研究其分型并与其他丙酸杆菌区分。C. acnes是人类皮肤重要的定植菌,参与维持皮肤健康,但也可能转变成为寻常痤疮的机会性病原菌。最新的研究显示,C. acnes不同型别间的平衡和与其他微生物的相互作用在寻常痤疮发生发展中发挥关键作用。本文综述C. acnes分型及其与寻常痤疮的相关性、药物敏感性和与其他微生物的相互作用。     

痤疮丙酸杆菌在寻常痤疮发病中的作用及其机制

痤疮丙酸杆菌(Propionibacterium acnes,现更名为 Cutibacterium acnes)是健康人群皮肤表面微生物群的主要成员之一,同时在寻常痤疮的疾病发生、发展过程中起到重要的作用.目前认为,寻常痤疮的发病主要包括皮脂腺异常分泌过盛、毛囊-皮脂腺单位表皮角化/脱落异常、炎症反应激活等主要环节.研...     

先天性角化不良与端粒酶、端粒相关基因的研究进展

先天性角化不良是一种具有遗传异质性的皮肤遗传病,其临床特征为黏膜白斑、甲营养不良、皮肤异色症、骨髓衰竭、肿瘤易感性以及其他系统损害.目前研究表明,其发病与端粒的长度缩短相关.端粒酶组分的基因突变可导致端粒酶活性的降低,使端粒缩短.概述引起端粒酶活性降低、端粒缩短的端粒酶组分的多个相关基因的研究进展,进一步阐明先天性角化不良的发病机制.

Abstract：

Dyskeratosis congenita (DC) is a rare skin disorder with heterogeneity, which is characterized by mucosal leukoplakia, nail dystrophy, abnormal skin pigmentation, bone marrow failure, cancer predisposition and other system damage. Currently, it is revealed that the pathogenesis of DC is related to the shortening of telomere length. Gene mutation of telomerase complex may result in a decline in telomerase activity and shortening of telomere length. This paper presents the advances in researches of telomerase complex genes responsible for reduction in telomerase activity and shortening of telomerase length, which may facilitate further elucidation of DC pathogenesis.     

痤疮丙酸杆菌致病机制研究进展

痤疮的发病机制较为复杂.研究表明,痤疮丙酸杆菌与痤疮的发生有重要的关系,在多个致病因素中起核心作用,然而痤疮丙酸杆菌在痤疮中的作用尚不完全清楚.随着医学研究的不断发展,痤疮丙酸杆菌基因功能的破解、痤疮丙酸杆菌生物膜致病耐药机制的不断完善、痤疮丙酸杆菌表面唾液酸酶为靶位的疫苗研发等为了解痤疮丙酸杆菌的致病机制和治疗提供线索.     

痤疮丙酸杆菌系统发育型及其在痤疮发病中作用研究进展

痤疮丙酸杆菌（C. acnes）为痤疮最重要致病菌,近年来随着对痤疮与C. acnes之间的研究深入,发现痤疮的发生与C. acnes的系统发育型密切相关。该文从C. acnes系统发育型不同分型与痤疮关系,C. acnes分型与其分泌的蛋白和胞外酶、Christie-Atkins-Munch-Petersen(CAMP)因子、卟啉及生物被膜等致病因素关系,以及促进炎症等方面进行总结归纳,更深刻和系统性地了解C. acnes,进一步了解C. acnes在痤疮发生发展中的重要作用,为有针对性地治疗痤疮,及相关药品及化妆品的开发提供更好的研究思路。     

免疫疗法在痤疮治疗中的研究进展

寻常痤疮(acne vulgaris)是一种多因素疾病。作为主要的致病因素之一,痤疮丙酸杆菌(Cutibacterium acnes,C.acnes,原Propionibacterium acnes,P.acnes)具有强烈的促炎活性,可以激活体内的固有免疫、体液免疫以及细胞免疫系统。痤疮丙酸杆菌在免疫激活中的关键作用为免疫疗法指引了方向,并且很可能成为解决痤疮丙酸杆菌的抗生素抗耐药问题的重要措施。近年来,包括痤疮丙酸杆菌疫苗,天然抗菌肽等多种免疫疗法不断被研究开发。本文将针对痤疮免疫疗法的最新研究进展,进行系统综述。     

痤疮丙酸杆菌与痤疮

痤疮丙酸杆菌的结构、分布和生理特点决定其在痤疮发病中的重要作用,尤其与痤疮的炎症损害及严重程度密切有关.目前,针对痤疮丙酸杆菌的痤疮治疗方法众多,包括应用四环素类、克林霉素、红霉素等治疗和过氧苯甲酰或5-氨基酮戊酸光动力疗法等.由于耐药性痤疮丙酸杆菌的出现,抗生素与非抗生素类药物的联合疗法已被证明为最佳治疗手段.痤疮丙酸杆菌全部基因组序列的测定使针对痤疮的菌苗疗法成为可能.     

痤疮丙酸杆菌与痤疮

痤疮丙酸杆菌的结构、分布和生理特点决定其在痤疮发病中的重要作用,尤其与痤疮的炎症损害及严重程度密切有关.目前,针对痤疮丙酸杆菌的痤疮治疗方法众多,包括应用四环素类、克林霉素、红霉素等治疗和过氧苯甲酰或5-氨基酮戊酸光动力疗法等.由于耐药性痤疮丙酸杆菌的出现,抗生素与非抗生素类药物的联合疗法已被证明为最佳治疗手段.痤疮丙酸杆菌全部基因组序列的测定使针对痤疮的菌苗疗法成为可能.     

Propionibacterium acnes stimulates pro-matrix metalloproteinase-2 expression through tumor necrosis factor-alpha in human dermal fibroblasts

Propionibacterium acnes (P. acnes) is a commensal microorganism found in sebum-rich skin and plays a role in acne inflammation by stimulating keratinocyte to produce a number of proinflammatory cytokines. However, the role of P. acnes in the dermis of acne lesions, where tissue remodeling after inflammation eventually takes place, is not known. In this study, we investigated whether P. acnes induces matrix metalloproteinase (MMP), a key enzyme involved in matrix remodeling in human dermal fibroblasts (hDF). We found that P. acnes increased expression of pro-matrix metalloproteinase (proMMP)-2 mRNA/protein in hDF, but not that of proMMP-9. Concomitantly, P. acnes induced tumor necrosis factor-alpha (TNF-alpha) mRNA/protein expression in hDF, which in turn increases both proMMP-2 mRNA and protein expression. P. acnes induced such changes through the activated NF-kappaB pathway. Doxycycline was found to inhibit the expression of proMMP-2 induced either by P. acnes or TNF-alpha. These results suggest that P. acnes stimulates hDF to produce TNF-alpha, which mediates the expression of proMMP-2 through the NF-kappaB pathway. The secretion of proMMP-2 from hDF upon P. acnes stimulation may contribute to the pathogenesis of tissue remodeling in acne skin.     

Correlation between Propionibacterium acnes biotypes, lipase activity and rash degree in acne patients

We examined the possible correlation between biotypes of Propionibacterium acnes, lipase activity, and rash degree in acne patients. Among 5 P. acnes biotypes, P. acnes biotype 3 (B3) was the most common, followed by P. acnes biotypes 1, 2 and 4; P. acnes biotype 5 was not found. P. acnes B3 was isolated from more severe skin rashes than those of the other biotypes. Production of propionic acid (PA) and butyric acid (BA) by P. acnes B3 was higher than those by the other P. acnes biotypes. As the rash degree in acne patients was more severe, the production of PA and BA elevated. Although only a few P. acnes strains were examined in the present study, P. acnes B3 had the highest lipase activity and might have the greatest influence on skin rash in acne patients.     

Staphylococcus aureus hijacks a skin commensal to intensify its virulence: immunization targeting β-hemolysin and CAMP factor

The need for a new anti-Staphylococcus aureus therapy that can effectively cripple bacterial infection, neutralize secretory virulence factors, and lower the risk of creating bacterial resistance is undisputed. Here, we propose what is, to our knowledge, a previously unreported infectious mechanism by which S. aureus may commandeer Propionibacterium acnes, a key member of the human skin microbiome, to spread its invasion and highlight two secretory virulence factors (S. aureus β-hemolysin and P. acnes CAMP (Christie, Atkins, Munch-Peterson) factor) as potential molecular targets for immunotherapy against S. aureus infection. Our data demonstrate that the hemolysis and cytolysis by S. aureus were noticeably augmented when S. aureus was grown with P. acnes. The augmentation was significantly abrogated when the P. acnes CAMP factor was neutralized or β-hemolysin of S. aureus was mutated. In addition, the hemolysis and cytolysis of recombinant β-hemolysin were markedly enhanced by recombinant CAMP factor. Furthermore, P. acnes exacerbated S. aureus-induced skin lesions in vivo. The combination of CAMP factor neutralization and β-hemolysin immunization cooperatively suppressed the skin lesions caused by coinfection of P. acnes and S. aureus. These observations suggest a previously unreported immunotherapy targeting the interaction of S. aureus with a skin commensal.     

Acne Vaccines: Therapeutic Option for the Treatment of Acne Vulgaris?

Acne, one of the most common skin diseases, is caused by multiple factors, including Propionibacterium acnes. Studies suggest that responses to P. acnes by host immunity play important roles in its pathogenesis. Identifying immune modulators that attenuate inflammatory responses against P. acnes and the inhibition of bacterial growth may lead to novel avenues of immunologic intervention.     

Relationship between Propionibacterium acnes biotypes and Jumi-haidoku-to

We examined the relationship between Propionibacterium acnes biotypes and Jumi-haidoku-to (JHT). In all the P. acnes strains tested, the production of propionic acid (PA) and butyric acid (BA) was suppressed in a medium containing 1 mg/ml JHT compared with the control medium without JHT. There were no significant differences in the rates of decreased PA and BA production between P. acnes biotype 3 (B3) and the other biotypes or between isolates from mild skin rash and more severe skin rash. P. acnes B3 was the most commonly identified biotype. The clinical effects on acne due to the anti-P. acnes lipase activity of JHT did not seem to be influenced by the degree of acne rash or the P. acnes biotype.     

Antibodies elicited by inactivated propionibacterium acnes-based vaccines exert protective immunity and attenuate the IL-8 production in human sebocytes: relevance to therapy for acne vulgaris

Propionibacterium acnes is a key pathogen involved in the progression of inflammation in acne vulgaris. We examined whether vaccination against P. acnes suppressed P. acnes-induced skin inflammation. Inactivation of P. acnes with heat was employed to create a P. acnes-based vaccine. Intranasal immunization in mice with this inactivated vaccine provoked specific antibodies against P. acnes. Most notably, immunization with inactivated vaccines generated in vivo protective immunity against P. acnes challenge and facilitated the resolution of ear inflammation in mice. In addition, antibodies elicited by inactivated vaccines effectively neutralized the cytotoxicity of P. acnes and attenuated the production of proinflammatory cytokine IL-8 in human sebocyte SZ95 cells. Intranasal immunization using heat-inactivated P. acnes-based vaccines provided a simple modality to develop acne vaccines. These observations highlight the concept that development of vaccines targeting microbial products may represent an alternative strategy to conventional antibiotic therapy.     

Lymphocyte transformation in subjects with nodulo-cystic acne

Patients with severe nodulo-cystic acne are known to have elevated serum antibody levels and increased immediate hypersensitivity reactions to Propionibacterium acnes. This organism is the predominant bacterium in normal pilosebaceous follicles of human skin, and can be consistently isolated from pustular lesions in acne. Previously it had been observed that delayed cutaneous hypersensitivity reactions to P. acnes were negative in patients with acne. The present study investigated the proliferative response of lymphocytes from patients with nodulo-cystic acne to phytohaemagglutinin (PHA) and P. acnes antigen stimulation. The response to PHA stimulation was within normal limits. The response to P. acnes antigen showed a significant increase over control values obtained by testing lymphocytes from acne-free subjects. Thus cell mediated immunity to P. acnes may be present in subjects with severe inflammatory acne. These findings raise the possibility that reactions to P. acnes may contribute to intensifying the inflammatory response in acne lesions.     

The effect of testosterone and anabolic steroids on the skin surface lipids and the population of Propionibacteria acnes in young postpubertal men

The effect of testosterone and anabolic steroids on skin surface lipids and the population of Propionibacteria acnes (P. acnes) was studied in power athletes. The subjects used self-administered high doses of testosterone and anabolic steroids during a 12-week strength training period. After 8 weeks' use of hormones the amount of dissolved skin surface lipids (SSL), and the Colony Forming Units/cm2 (CFU/cm2) of P. acnes had increased (p less than 0.01). The percentage values of dissolved SSL constituents changed. The cholesterol (CHO) and also the relative values of free fatty acids (FFA) increased. SSL constituents obtained by collection on absorbent paper likewise changed the dissolved constituents. It was concluded that high doses of testosterone and anabolic steroids may increase the SSL, the P. acnes population, and the percentage of the CHO and FFA of the skin surface lipids in healthy young men.     

The aerobic growth of Propionibacterium acnes in primary cultures from skin.

Although Propionibacterium acnes ordinarily grows as an anaerobe, this organism was commonly seen on aerobic primary cultures (directly from skin) of the forehead, axilla, deltoid area, and antecubital fossa. On subculture, strains from aerobic primary cultures showed their normal anaerobic state. On repeated tests of the foreheads of 7 subjects over periods of 1 to 4 yr, 24% of all cultures were positive for propionibacteria (P. acnes) on aerobic culture. This phenomenon was equally common in cultures from those with relatively sparse or dense populations of P. acnes on the skin surface. Several different patterns of aerobic growth were observed: satellitism, profuse growth at one dilution and none on the next higher dilution, and proportionate growth in successive dilutions. These different growth patterns indicate that more than one mechanism is operative in stimulating the aerobic growth of propionibacteria. Whether one or more of these mechanisms is operative in vivo, we do not know, but it appears that they do not account for the great individual differences in population density of P. acnes on such sites as the forehead.     

Delayed skin test reactivity to Propionibacterium acnes correlates with severity of inflammation in acne vulgaris

Propiontibacterium acnes is the bacterial species most consistently isolated from acne lesions. Intradermal injection of a heat-killed suspension of P. acnes induced a delayed erythematous and often papular inflammatory reaction which was maximal after 24–48 h. This response was dose related and was probably mediated at least partly by immune mechanisms. In eighty-one subjects with acne of varying severity the intensity of the 48 h skin test reaction was significantly related to the severity of the acne. These findings indicate that the host response to P. acnes is an important variable in determining the severity of inflammatory acne.