Pathways to inflammation: Acne pathophysiology

European Journal of Dermatology

Volumn 21, Issue 3, 2011, Pages 323-333

  Taylor, Marisa ^a   Gonzalez, Maria ^a   Porter, Rebecca ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

Acne; Androgens; Cytokines; Diet; Genetics; Inflammation; Propionibacterium acnes; Sebaceous glands

Indexed keywords

ALANINE; ANDROGEN; CYCLOSPORIN; CYSTEINE; DEFENSIN; GLYCINE; SKIN LIPID;

ACNE; ACNE VULGARIS; ANDROGEN SYNTHESIS; BACTERIAL SKIN DISEASE; DIETARY INTAKE; DISEASE ACTIVITY; DISEASE COURSE; DISEASE SEVERITY; DNA POLYMORPHISM; FOOD COMPOSITION; GENETIC SUSCEPTIBILITY; GLYCEMIC INDEX; HUMAN; IMMUNOSTIMULATION; INNATE IMMUNITY; NONHUMAN; PATHOGENESIS; PATHOPHYSIOLOGY; PROPIONIBACTERIUM ACNES; PROTEIN FUNCTION; REVIEW; SCAR; SEBACEOUS GLAND DISEASE; SEBUM SECRETION; SKIN INFLAMMATION;

ACNE VULGARIS; GENETIC PREDISPOSITION TO DISEASE; HUMANS; INFLAMMATION; SKIN;

EID: 79960802581     PISSN: 11671122     EISSN: 19524013     Source Type: Journal    
DOI: 10.1684/ejd.2011.1357     Document Type: Review

References (154)

1. Goulden, Mcgeown, Cunliffe. The familial risk of adult acne: a comparison between first-degree relatives of affected and unaffected individuals. Br J Dermatol 1999; 141: 297-300.
2. White GM. Recent findings in the epidemiologic evidence, classification, and subtypes of acne vulgaris. J Am Acad Dermatol 1998; 39: S34-7.
3. Abdel-Hafez K, Mahran AM, Hofny ERM, Mohammed KA, Darweesh AM, Aal AA. The impact of acne vulgaris on the quality of life and psychologic status in patients from upper Egypt. Int J Dermatol 2009; 48: 280-5.
4. Jeremy AHT, Holland DB, Roberts SG, Thomson KF, Cunliffe WJ. Inflammatory events are involved in acne lesion initiation. J Invest Dermatol 2003; 121: 20-7.
5. Zouboulis CC. Is acne vulgaris a genuine inflammatory disease? Dermatology 2001; 203: 277-9.
6. Pawin H, Beylot C, Chivot M, et al. Physiopathology of acne vulgaris: recent data, new understanding of the treatments. Eur J Dermatol 2004; 14: 4-12.
7. Kurokawa I, Danby FW, Ju Q, et al. New developments in our understanding of acne pathogenesis and treatment. Exp Dermatol 2009; 18: 821-2.
8. Holland DB, Jeremy AHT. The role of inflammation in the pathogenesis of acne and acne scarring. Seminars in Cutaneous Medicine and Surgery 2005; 24: 79-83.
9. Farrar MD, Ingham E. Acne: Inflammation. Clin Dermatol 2004; 22: 380-4.
10. Cunliffe WJ, Holland DB, Clark SM, Stables GI. Comedogenesis: some new aetiological, clinical and therapeutic strategies. Br J Dermatol 2000; 142: 1084-91.
11. Kligman AM. An overview of acne. J Investig Dermatol 1974; 62: 268-87.
12. Zouboulis CC, Eady A, Philpott M, et al. What is the pathogenesis of acne? Experimental Dermatology 2005; 14: 143.
13. Thiboutot D, Bayne E, Thorne J, et al. Immunolocalization of 5-alpha reductase isozymes in acne lesions and normal skin. Arch Dermatol 2000; 136: 1125-9.
14. Kupper TS. The activated keratinocyte: A model for inducible cytokine production by non-bone-marrow-derived cells in cutaneous inflammatory and immune responses. Investig Dermatol 1990; 94: 146s-150s.
15. Anttila HSI, Reitamo S, Erko P, Miettinen A, Didierjean L, Saurat J-H. Membrane and cytosolic interleukin-1 alpha and beta in normal human epidermal cells: variability of epitope exposure in immunohistochemistry. J Invest Dermatol 1990; 95: 31-8.
16. Anttila HSI, Reitamo S, Saurat J-H. Interleukin 1 immunoreactivity in sebaceous glands. Br J Dermatol 1992; 127: 585-8.
17. Ingham E, Eady EA, Goodwin CE, Cove JH, Cunliffe WJ. Pro-Inflammatory levels of Interleukin-1 alpha-like bioactivity are present in the majority of open comedones in acne vulgaris. J Investig Dermatol 1992; 98: 895-901.
18. Ingham E, Walters CE, Eady EA, Cove JH, Kearney JN, Cunliffe WJ. Inflammation in acne vulgaris: failure of skin micro-organisms to modulate keratinocyte interleukin-1 alpha production in vitro. Dermatology 1998: 86-8.
19. Kim J, Ochoa M-T, Krutzik SR, et al. Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol 2002; 169: 1535-41.
20. Oeff MK, Seltmann H, Hiroi N, et al. Differential regulation of toll-like receptor and CD14 pathways by retinoids and corticosteroids in human sebocytes. Dermatology 2006; 213: 266.
21. Kadowaki N, Ho S, Antonenko S, et al. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med 2001; 194: 863-70.
22. Jugeau S, Tenaud I, Knol AC, et al. Induction of toll-like receptors by Propionibacterium acnes. Br J Dermatol 2005; 153: 1105-13.
23. Chen W, Thiboutot D, Zouboulis CC. Cutaneous androgen metabolism: basic research and clinical perspectives. JID 2002; 119: 992-1007.
24. Zouboulis CC. Acne and sebaceous gland function. Clin Dermatol 2004; 22: 360-6.
25. Alestas T, Ganceviciene R, Fimmel S, Müller-Decker K, Zouboulis C. Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands. J Mol Med 2006; 84: 75-87.
26. Makrantonaki E, Zouboulis CC. Testosterone metabolism to 5-alpha dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes. Br J Dermatol 2007; 156: 428-32.
27. Trivedi NR, Cong Z, Nelson AM, et al. Peroxisome proliferatoractivated receptors increase human sebum production. J Invest Dermatol 2006; 126: 2002-9.
28. Rosenfield RL, Kentsis A, Deplewski D, Ciletti N. Rat preputial sebocyte differentiation involves peroxisome proliferator-activated receptors. JID 1999; 112: 226-32.
29. Schuster M, Zouboulis CC, Ochsendorf F, et al. Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: a new treatment modality for acne? Br J Dermatol 2011; 164: 182-6.
30. Lee WJ, Jung HD, Lee HJ, et al. Influence of substance-P on cultured sebocytes. Arch Dermatol Res 2008; 300: 311-6.
31. Toyoda M, Nakamura M, Makino T, Kagoura M, Morohashi M. Sebaceous glands in acne patients express high levels of neutral endopeptidase. Exp Dermatol 2002; 11: 241-7.
32. Papakonstantinou E, Aletras AJ, Glass E, et al. Matrix metalloproteinases of epithelial origin in facial sebum of patients with acne and their regulation by isotretinoin. J Investig Dermatol 2005; 125: 673-84.
33. Caillon F, O'Connell M, Eady EA, et al. Interleukin-10 secretion from CD14+ peripheral blood mononuclear cells is downregulated in patients with acne vulgaris. Br J Dermatol 2010; 162: 296-303.
34. Suh DH, Kwon TE, Youn JI. Changes of comedonal cytokines and sebum secretion after UV irradiation in acne patients. Eur J Dermatol 2002; 12: 139-44.
35. Holland DB, Jeremy AHT, Roberts SG, Seukeran DC, Layton AM, Cunliffe WJ. Inflammation in acne scarring: a comparison of the responses in lesions from patients prone and not prone to scar. Br J Dermatol 2004; 150: 72-81.
36. Youn SW, Park ES, Lee DH, Huh CH, Park KC. Does facial sebum excretion really affect the development of acne? Br J Dermatol 2005; 153: 919-24.
37. Hamilton JB, Mestler GE. Effect of orchiectomy and oophorectomy upon existent and potential acne. J Invest Dermatol 1963; 41: 249-53.
38. Pochi PE, Strauss JS, Mescon H. Sebum secretion and urinary fractional 17-ketosteroid and total 17-hydroxycorticoid excretion in male castrates. J Invest Dermatol 1962; 39: 475-83.
39. Pochi PE, Strauss JS. Sebum production, casual sebum levels, titratable acidity of sebum, and urinary fractional 17-ketosteroid excretion in males with acne. J Invest Dermatol 1964; 43: 383-8.
40. Wisniewski AB, Migeon CJ, Meyer-Bahlburg HFL, et al. Complete androgen insensitivity syndrome: Long-term medical, surgical, and psychosexual outcome. J Clin Endocrinol Metab 2000; 85: 2664-9.
41. Imperato-McGinley J, Gautier T, Cai L, Yee B, Epstein J, Pochi P. The androgen control of sebum production. Studies of subjects with dihydrotestosterone deficiency and complete androgen insensitivity. J Clin Endocrinol Metab 1993; 76: 524-8.
42. Chen W, Tsai S-J, Sheu H-M, Tsai J-C, Zouboulis CC. Testosterone synthesized in cultured human SZ95 sebocytes derives mainly from dehydroepiandrosterone. Exp Dermatol 2010; 19: 470-2.
43. Carmina E, Godwin A, Stanczyk F, Lippman J, Lobo R. The association of serum androsterone glucuronide with inflammatory lesions in women with adult acne. J Endocrinol Invest 2002; 25: 765-8.
44. Lucky AW, Biro FM, Simbartl LA, Morrison JA, Sorg NW. Predictors of severity of acne vulgaris in young adolescent girls: Results of a five-year longitudinal study. J Pediatr 1997; 130: 30-9.
45. Seirafi H, Farnaghi F, Vasheghani-Farahani A, et al. Assessment of androgens in women with adult-onset acne. Int J Dermatol 2007; 46: 1188-91.
46. Aizawa H, Niimura M. Elevated serum insulin-like growth factor-1 (IGF-1) levels in women with postadolescent acne. J Dermatol 1995; 22: 249-52.
47. Thiboutot D, Gilliland K, Light J, Lookingbill D. Androgen metabolism in sebaceous glands from subjects with and without acne. Arch Dermatol 1999; 135: 1041-5.
48. Holland DB, Gowland G, Cunliffe WJ. Sex-linked differences in acne vulgaris. Acta Derm Venereol 1985; 65: 551-3.
49. Wei B, Pang Y, Zhu H, et al. The epidemiology of adolescent acne in North East China. Eur Acad Dermatol Venereol 2010; 9999.
50. Yang Z, Yu H, Cheng B, et al. Relationship between the CAG repeat polymorphism in the androgen receptor gene and acne in the Han ethnic group. Dermatology 2009; 218: 302-6.
51. Zouboulis CC. The human skin as a hormone target and an endocrine gland. Hormones (Athens) 2004; 3: 9-26.
52. Weinstein Y, Ran S, Segal S. Sex-associated differences in the regulation of immune responses controlled by the MHC of the mouse. J Immunol 1984; 132: 656-61.
53. Thiboutot D, Jabara S, McAllister JM, et al. Human skin is a steroidogenic tissue: Steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1). J Invest Dermatol 2003; 120: 905-14.
54. Chen W, Yang CC, Liao CY, et al. Expression of sex-determining genes in human sebaceous glands and their possible role in the pathogenesis of acne. Journal of the European Academy of Dermatology & Venereology 2006; 20: 846-52.
55. Liang T, Hoyer S, Yu R, et al. Immunocytochemical localization of androgen receptors in human skin using monoclonal antibodies against the androgen receptors. J Investig Dermatol 1993; 100: 663-6.
56. Thiboutot DM, Knaggs H, Gilliland K, Hagari S. Activity of type 1 5-alpha reductase is greater in the follicular infrainfundibulum compared with the epidermis. Br J Dermatol 1997; 136: 166-71.
57. Thiboutot D, Harris G, Iles V, Cimis G, Gilliland K, Hagari S. Activity of the type 1 5α-reductase exhibits regional differences in isolated sebaceous glands and whole skin. J Investig Dermatol 1995; 105: 209-14.
58. Fritsch M, Orfanos CE, Zouboulis CC. Sebocytes are the key regulators of androgen homeostasis in human skin. J Investig Dermatol 2001; 116: 793-800.
59. Thiboutot D, Knaggs H, Gilliland K, Lin G. Activity of 5-alpha-reductase and 17-beta-hydroxysteroid dehydrogenase in the infrainfundibulum of subjects with and without acne vulgaris. Dermatology 1998; 196: 38-42.
60. Thiboutot D, Martin P, Volikos L, Gilliland K. Oxidative activity of the type 2 isozyme of 17beta-hydroxysteroid dehydrogenase (17beta-HSD) predominates in human sebaceous glands. JID 1998; 111: 390-5.
61. Thiboutot D. Regulation of human sebaceous glands. J Investig Dermatol 2004; 123: 1-12.
62. Zouboulis CC, Xia L, Akamatsu H, et al. The human sebocyte culture model provides new insights into development and management of seborrhoea and acne. Dermatology 1998; 196: 21-31.
63. Thornton MJ, Thornton MJ. The biological actions of estrogens on skin. Exp Dermatol 2002; 11: 487-502.
64. Pelle E, McCarthy J, Seltmann H, et al. Identification of histamine receptors and reduction of squalene levels by an antihistamine in sebocytes. J Invest Dermatol 2007; 128: 1280-5.
65. Chen W, Tsai SJ, Wang CA, Tsai JC, Zouboulis CC. Human sebocytes express prostaglandin E2 receptors EP2 and EP4 but treatment with prostaglandin E2 does not affect testosterone production. Br J Dermatol 2009; 161: 674-7.
66. Ganceviciene R, Graziene V, Fimmel S, Zouboulis CC. Involvement of the corticotropin-releasing hormone system in the pathogenesis of acne vulgaris. Br J Dermatol 2009; 160: 345-52.
67. Kono M, Nagata H, Umemura S, Kawana S, Osamura RY. In situ expression of corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) genes in human skin. The FASEB Journal. 2001; 15: 2297-9.
68. Toyoda M, Nakamura M, Morohashi M. Neuropeptides and sebaceous glands. Eur J Dermatol 2002; 12: 422-7.
69. Chen W, Yang C-C, Sheu H-M, Seltmann H, Zouboulis CC. Expression of peroxisome proliferator-activated receptor and CCAAT/enhancer binding protein transcription factors in cultured human sebocytes. J Invest Dermatol 2003; 121: 441-7.
70. Bohm M, Metze D, Schulte U, Becher E, Luger TA, Brzoska T. Detection of melanocortin-1 receptor antigenicity on human skin cells in culture and in situ. Exp Dermatol 1999; 8: 453-61.
71. Bohm M, Schiller M, Stander S, et al. Evidence for Expression of Melanocortin-1 Receptor in Human Sebocytes In Vitro and In Situ. J Invest Dermatol 2002; 118: 533-9.
72. Ganceviciene R, Graziene V, Bohm M, Zouboulis CC. Increased in situ expression of melanocortin-1 receptor in sebaceous glands of lesional skin of patients with acne vulgaris. Exp Dermatol 2007; 16: 547-52.
73. Stewart ME. Sebaceous gland lipids. Seminars in Dermatology 1992; 11: 100-5.
74. Makrantonaki E, Adjaye J, Herwig R, et al. Age-specific hormonal decline is accompanied by transcriptional changes in human sebocytes in vitro. Aging Cell 2006; 5: 331-44.
75. Sansone-Bazzano G, Cummings B, Seeler AK, Reisner RM. Differences in the lipid constituents of sebum from pre-pubertal and pubertal subjects. Br J Dermatol 1980; 103: 131-7.
76. Zouboulis CC, Schagen S, Alestas T. The sebocyte culture: a model to study the pathophysiology of the sebaceous gland in sebostasis, seborrhoea and acne. Arch Dermatol Res 2008; 300: 397-413.
77. Cossette C, Patel P, Anumolu JR, et al. Human neutrophils convert the sebum-derived polyunsaturated fatty acid sebaleic acid to a potent granulocyte chemoattractant. J Biol Chem 2008; 283: 11234-43.
78. Stewart ME, Downing DT, Cook JS, Hansen JR, Strauss JS. Sebaceous gland activity and serum dehydroepiandrosterone sulfate levels in boys and girls. Arch Dermatol 1992; 128: 1345-8.
79. Mourelatos K, Eady EA, Cunliffe WJ, Clark SM, Cove JH. Temporal changes in sebum excretion and propionibacterial colonization in preadolescent children with and without acne. Br J Dermatol 2007; 156: 22-31.
80. Lee D-Y, Huang C-M, Nakatsuji T, et al. Histone H4 Is a major component of the antimicrobial action of human sebocytes. J Invest Dermatol 2009; 129: 2489-96.
81. Nakatsuji T, Kao MC, Fang J-Y, et al. Antimicrobial property of lauric acid against Propionibacterium acnes: its therapeutic potential for inflammatory acne vulgaris. J Invest Dermatol 2009; 129: 2480-8.
82. Nagy I, Pivarcsi A, Kis K, et al. Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes. Microbes Infect 2006; 8: 2195-205.
83. Nakatsuji T, Kao MC, Zhang L, Zouboulis CC, Gallo RL, Huang C-M. Sebum free fatty acids enhance the innate immune defense of human sebocytes by upregulating β-defensin-2 expression. J Invest Dermatol 2010; 130: 985-94.
84. Lee D-Y, Yamasaki K, Rudsil J, et al. Sebocytes express functional cathelicidin antimicrobial peptides and can act to kill Propionibacterium acnes. J Invest Dermatol 2008; 128: 1863-6.
85. Cordain L, Lindeberg S, Hurtado M, Hill K, Eaton SB, Brand-Miller J. Acne Vulgaris: A Disease of Western Civilization. Arch Dermatol 2002; 138: 1584-90.
86. Shepherd PR. Secrets of insulin and IGF-1 regulation of insulin secretion revealed. Biochem J 2004; 377: e1-e2.
87. Melnik BC, Schmitz G. Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Exp Dermat 2009; 18: 833-41.
88. Smith TM, Gilliland K, Clawson GA, Thiboutot D. IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase/Akt pathway. J Invest Dermatol 2008; 128: 1286-93.
89. Cappel M, Mauger D, Thiboutot D. Correlation between serum levels of insulin-like growth factor 1, dehydroepiandrosterone sulfate, and dihydrotestosterone and acne lesion counts in adultWomen. Arch Dermatol 2005; 141: 333-8.
90. Smith RN, Braue A, Varigos GA, Mann NJ. The effect of a low glycemic load diet on acne vulgaris and the fatty acid composition of skin surface triglycerides. J Dermatol Sc 2008; 50: 41-52.
91. Vora S, Ovhal A, Jerajani H, Nair N, Chakrabortty A. Correlation of facial sebum to serum insulin-like growth factor-1 in patients with acne. Br J Dermatol 2008; 159: 990-1.
92. Pappas A, Anthonavage M, Gordon JS. Metabolic fate and selective utilization of major fatty acids in human sebaceous gland. J Invest Dermatol 2002; 118: 164-71.
93. Katsuta Y, Iida T, Inomata S, Denda M. Unsaturated fatty acids induce calcium influx into keratinocytes and cause abnormal differentiation of epidermis. J Investig Dermatol 2005; 124: 1008-13.
94. Katsuta Y, Iida T, Hasegawa K, Inomata S, Denda M. Function of oleic acid on epidermal barrier and calcium influx into keratinocytes is associated with N-methyl d-aspartate-type glutamate receptors. Br J Dermatol 2009; 160: 69-74.
95. Leyden JJ, McGinley KJ, Mills OH, Kligman AM. Propionibacterium levels in patients with and without acne vulgaris. J Investig Dermatol 1975; 65: 382-4.
96. Leyden JJ, McGiley KJ, Mills OH, Kligman AM. Age-related changes in the resident bacterial flora of the human face. J Investig Dermatol 1975; 65: 379-81.
97. McGinley KJ, Webster GF, Ruggieri MR, Leyden JJ. Regional variations in density of cutaneous propionibacteria: correlation of Propionibacterium acnes populations with sebaceous secretion. J Clin Microbiol 1980; 12: 672-5.
98. Jappe U, Ingham E, Henwood J, Holland KT. Propionibacterium acnes and inflammation in acne; P. acnes has T-cell mitogenic activity. Br J Dermatol 2002; 146: 202-9.
99. Coates P, Vyakrnam S, Eady EA, Jones CE, Cove JH, Cunliffe WJ. Prevalence of antibiotic-resistant propionibacteria on the skin of acne patients: 10-year surveillance data and snapshot distribution study. Br J Dermatol 2002; 146: 840-8.
100. Eady EA, Cove JH, Holland KT, Cunliffe WJ. Erythromycin resistant propionibacteria in antibiotic treated acne patients: association with therapeutic failure. Br J Dermatol 1989; 121: 51-7.
101. Leyden JJ, McGinley KJ, Cavalieri S, Webster GF, Mills OH, Kligman AM. Propionibacterium acnes resistance to antibiotics in acne patients. J Am Acad Dermatol 1983; 8: 41-5.
102. Burkhart CG, Burkhart CN. Expanding the microcomedone theory and acne therapeutics: Propionibacterium acnes biofilm produces biological glue that holds corneocytes together to form plug. J Am Acad Dermatol 2007; 57: 722-4.
103. Burkhart CN, Burkhart CG. Microbiology's principle of biofilms as a major factor in the pathogenesis of acne vulgaris. Int J Dermatol 2003; 42: 925-7.
104. Burkhart CN, Gottwald L. Assessment of etiologic agents in acne pathogenesis. Skinmed 2003; 2: 222-8.
105. Coenye T, Peeters E, Nelis HJ. Biofilm formation by Propionibacterium acnes is associated with increased resistance to antimicrobial agents and increased production of putative virulence factors. Res Microbiol 2007; 158: 386-92.
106. Coates T, Eady A, Cove J. Propionibacterial biofilms cannot explain antibiotic resistance but might contribute to some cases of antibiotic recalcitrant acne. Br J Dermatol 2003; 148: 366-7.
107. Bek-Thomsen M, Lomholt HB, Kilian M. Acne is not associated with yet-uncultured bacteria. J Clin Microbiol 2008; 46: 3355-60.
108. Miura Y, Ishige I, Soejima N, et al. Quantitative PCR of Propionibacterium acnes DNA in samples aspirated from sebaceous follicles on the normal skin of subjects with or without acne. J Med Dent Sci 2010; 57: 65-74.
109. Ammad S, Gonzales M, Edwards C, Finlay AY, Mills C. An assessment of the efficacy of blue light phototherapy in the treatment of acne vulgaris. J Cosmet Dermatol 2008; 7: 180-8.
110. Esterly NB, Furey NL, Flanagan LE. The effect of antimicrobial agents on leukocyte chemotaxis. J Investig Dermatol 1978; 70: 51-5.
111. Webster GF, McGinley KJ, Leyden JJ. Inhibition of lipase production in Propionibacterium acnes by sub-minimal-inhibitory concentrations of tetracycline and erythromycin. British Journal of Dermatology 1981; 104: 453-7.
112. Simonart T, Dramaix M, Maertelaer VD. Efficacy of tetracyclines in the treatment of acne vulgaris: a review. Br J Dermatol 2008; 158: 208-16.
113. Sainte-Marie I, Tenaud I, Jumbou O, Dreno B. Minocycline modulation of alpha-MSH production by keratinocytes in vitro. Acta Dermato-Venereologica 1999; 79: 265-7.
114. Nagy I, Pivarcsi A, Koreck A, Szell M, Urban E, Kemeny L. Distinct strains of Propionibacterium acnes induce selective human β-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors. J Investig Dermatol 2005; 124: 931-8.
115. Zouboulis CC. Propionibacterium acnes and sebaceous lipogenesis: A love-hate relationship?. Invest Dermatol 2009; 129: 2093-6.
116. Liu AY, Destoumieux D, Wong AV, et al. Human β-defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation. J Invest Dermatol 2002; 118: 275-81.
117. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol 2003; 3: 710-20.
118. Schlapbach C, Yawalkar N, Hunger RE. Human β-defensin-2 and psoriasin are overexpressed in lesions of acne inversa. J Am Acad Dermatol 2009; 61: 58-65.
119. Kolls JK, McCray PB, Chan YR. Cytokine-mediated regulation of antimicrobial proteins. Nat Rev Immunol 2008; 8: 829-35.
120. Liu L, Roberts AA, Ganz T. By IL-1 signaling, monocyte-derived cells dramatically enhance the epidermal antimicrobial response to lipopolysaccharide. J Immunol 2003; 170: 575-80.
121. Harder J, Bartels J, Christophers E, Schroder JM. A peptide antibiotic from human skin. Nature 1997; 387: 861.
122. Georgel P, Crozat K, Lauth X, et al. A toll-like receptor 2-responsive lipid effector pathway protects mammals against skin infections with gram-positive bacteria. Infect Immun 2005; 73: 4512-21.
123. Gariboldi S, Palazzo M, Zanobbio L, et al. Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of β-defensin 2 via TLR2 and TLR4. J Immunol 2008; 181: 2103-10.
124. Bojar RA, Holland KT. Acne and propionibacterium acnes. Clinics in Dermatology 2004; 22: 375-9.
125. Sugisaki H, Yamanaka K, Kakeda M, et al. Increased interferon-α, interleukin-12p40 and IL-8 production in Propionibacterium acnes-treated peripheral blood mononuclear cells from patient with acne vulgaris: Host response but not bacterial species is the determinant factor of the disease. Journal of Dermatological Science 2009; 55: 47-52.
126. Ballanger F, Baudry P, N'Guyen J M, Khammari A, Dreno B. Heredity: a prognostic factor for acne. Dermatology 2006; 212: 145-9.
127. Ghodsi SZ, Orawa H, Zouboulis CC. Prevalence, severity and severity risk factors of acne in high school pupils: a community-based study. J Invest Dermatol 2009; 129: 2136-41.
128. Xu S, Wang H, Fan X, et al. The familial risk of acne vulgaris in Chinese Hans-a case-control study. J Eur Acad Dermatol Venereol 2007; 21: 602-5.
129. Bataille V, Snieder H, MacGregor AJ, Sasieni P, Spector TD. The influence of genetics and environmental factors in the pathogenesis of acne: A twin study of acne in women. JID 2002; 119: 1317-22.
130. Pang Y, He C, Liu Y, et al. Combination of short CAG and GGN repeats in the androgen receptor gene is associated with acne risk in North East China. Journal of the European Academy of Dermatology and Venereology 2008; 22: 1445-51.
131. Sawaya ME, Shalita AR. Androgen receptor polymorphisms (CAG repeat lengths) in androgenetic alopecia, hirsutism, and acne. J Cutan Med Surg 1998; 3: 9-15.
132. Szabo K, Tax G, Teodorescu-Brizeu D, Koreck A, Kemeny L. TNFα gene polymorphisms in the pathogenensis of acne vulgaris. Arch Dermatol Res 2010; 9999.
133. Baz K, Emin Erdal M, Yazi{dotless}ci{dotless} A, et al. Association between tumor necrosis factor-alpha gene promoter polymorphism at position-308 and acne in Turkish patients. Arch Dermatol Res 2008; 300: 371-6.
134. Tian LM, Xie HF, Yang T, Hu YH, Li J, Wang WZ. Association Study of Tumor Necrosis Factor Receptor Type 2 M196R and Toll-Like Receptor 2 Arg753Gln Polymorphisms with Acne Vulgaris in a Chinese Han Ethnic Group. Dermatology 2010; 221: 276-84.
135. Szabó K, Tax G, Kis K, et al. Interleukin-1A +4845(G> T) polymorphism is a factor predisposing to acne vulgaris. Tissue Antigens 2010; 76: 411-5.
136. Herane MI, Ando I. Acne in infancy and acne genetics. Dermatology 2003; 206: 24-8.
137. Paraskevaidis A, Drakoulis N, Roots I, Orfanos CE, Zouboulis CC. Polymorphisms in the human cytochrome P-450 1A1 gene (CYP1A1) as a factor for developing acne. Dermatology 1998; 196: 1715.
138. He L, Yang Z, Yu H, et al. The relationship between CYP17-34T/C polymorphism and acne in Chinese subjects revealed by sequencing. Dermatology 2006; 212: 338-42.
139. Ostlere LS, Rumsby G, Holownia P, Jacobs HS, Rustin MHA, Honour JW. Carrier status for steroid 21-hydroxylase deficiency is only one factor in the variable phenotype of acne. Clinical Endocrinology 1998; 48: 209-15.
140. Munro CS, Wilkie AOM. Epidermal mosaicism producing localised acne: somatic mutation in FGFR2. The Lancet 1998; 352: 704-5.
141. Katoh M. FGFR2 abnormalities underlie a spectrum of bone, skin, and cancer pathologies. J Invest Dermatol 2009; 129: 1861-7.
142. Melnik B, Schmitz G. FGFR2 signaling and the pathogenesis of acne. Journal der Deutschen Dermatologischen Gesellschaft 2008; 6: 721-8.
143. Melnik BC, Schmitz G, Zouboulis CC. Anti-acne agents attenuate FGFR2 signal transduction in acne. J Invest Dermatol 2009; 129: 1868-77.
144. Hanchard N, Elzein A, Trafford C, et al. Classical sickle betaglobin haplotypes exhibit a high degree of long-range haplotype similarity in African and Afro-Caribbean populations. BMC Genetics 2007; 8: 52.
145. Bloom DF. Is acne really a disease?: a theory of acne as an evolutionarily significant, high-order psychoneuroimmune interaction timed to cortical development with a crucial role in mate choice. Medical Hypotheses 2004; 62: 462-9.
146. Yazdabadi A, Magee J, Harrison S, Sinclair R. The Ludwig pattern of androgenetic alopecia is due to a hierarchy of androgen sensitivity within follicular units that leads to selective miniaturization and a reduction in the number of terminal hairs per follicular unit. Br J Dermatol 2008; 159: 1300-2.
147. Aldana OL, Holland DB, Cunliffe WJ. Variation in pilosebaceous duct keratinocyte proliferation in acne patients. Dermatology 1998; 196: 98-9.
148. Hughes BR, Morris C, Cunliffe WJ, Leigh IM. Keratin expression in pilosebaceous epithelia in truncal skin of acne patients. Br J Dermatol 1996; 134: 247-56.
149. Freedberg IM, Tomic-Canic M, Komine M, Blumenberg M. Keratins and the keratinocyte activation cycle. J Invest Dermatol 2001; 116: 633-40.
150. Marsland AM, Griffiths CE. The macrolide immunosuppressants in dermatology: mechanisms of action. Eur J Dermatology 2002; 12: 618-22.
151. Strahan JE, Burch JM. Cyclosporine-Induced Infantile Nodulocystic Acne. Arch Dermatol 2009; 145: 797-9.
152. Ciftci S. Topical cyclosporine treatment in inflammatory nodular acne. European journal of dermatology. Eur J Dermatol 2008; 18: 716-7.
153. Nelson AM, Gilliland KL, Cong Z, Thiboutot DM. 13-cis retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. J Invest Dermatol 2006; 126: 2178-89.
154. Leyden JJ, McGinley KJ, Foglia AN. Qualitative and quantitative changes in cutaneous bacteria associated with systemic isotretinoin therapy for acne conglobata. J Investig Dermatol 1986; 86: 390-3.