Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes

Abstract

Acne is a common skin disorder of the pilosebaceous unit. In addition to genetic, hormonal and environmental factors, abnormal colonization by Propionibacterium acnes has been implicated in the occurrence of acne via the induction of inflammatory mediators. To gain more insight into the role that sebocytes play in the innate immune response of the skin, particularly in acne, we compared the antimicrobial peptide and proinflammatory cytokine/chemokine expression at mRNA and protein levels, as well as the viability and differentiation of SZ95 sebocytes in response to co-culture with representative isolates of P. acnes type IA and type IB as well as Escherichia coli-derived lipopolysaccharide (LPS). We found that, in vitro, P. acnes type IA and IB isolates and LPS induced human beta-defensin-2 and proinflammatory cytokine/chemokine expression, and influenced sebocyte viability and differentiation. Our results provide evidence that sebocytes are capable of producing proinflammatory cytokines/chemokines and antimicrobial peptides, which may have a role in acne pathogenesis. Furthermore, since P. acnes types IA and IB differentially affect both the differentiation and viability of sebocytes, our data demonstrate that different strains of P. acnes vary in their capacity to stimulate an inflammatory response within the pilosebaceous follicle.

An update on the role of the sebaceous gland in the pathogenesis of acne

“…It is known that P. acnes-induced cytokine production is mediated by Toll-like receptor (TLR) 2. [87][88][89][90] The pilosebaceous unit is an immunocompetent organ. Keratinocytes and sebocytes may act as immune cells capable of pathogen recognition and abnormal lipid presentation.…”

“…93 Cathelicidin and hBD-2 are detected in cultured human sebocytes, the predominant cells residing in the sebaceous gland, and their expression levels are upregulated in the presence of P. acnes. 89,94 Each P. acnes strain has been shown to influence sebocyte viability and differentiation differently, a fact that raises the possibility that certain P. acnes strains to be responsible for opportunistic infections worsening acne lesions. 89,94,95 A description of phylogenetically distinct P. acnes clusters has been already undertaken.…”

“…89 There is a difference in the cytokine production curve over time after treatment between P. acnes and LPS. While LPS stimulates CXCL8, TNFα and IL-1α, P. acnes stimulates CXCL8 and TNFα only.…”

Variable expression of immunoreactive surface proteins of Propionibacterium acnes

“…P. acnes can also promote the synthesis of IL-18, which, in the presence of IL-12, is a pivotal mediator of the Th1 cytokine response (Braga et al, 2003;Matsui et al, 1997). Type 1A and 1B P. acnes have also been shown to induce proinflammatory/chemokine secretion in a sebocyte cell line (Nagy et al, 2006). In addition, antibiotic resistance in P. acnes has been associated with therapeutic failure in the treatment of acne vulgaris (Eady et al, 1989) and is increasingly becoming a widespread phenomenon (Eady et al, 2003).…”

Innate Immune Defense System of the Skin

“…46,47 Cathelicidin expression levels are upregulated in the presence of Gram-positive bacteria. 48,49 LL-37 is induced within the epidermis during the development of verruca vulgaris. 50 Cutaneous injury induces the release of cathelicidin active against group A Streptococcus.…”