Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL

Graham, Gillian M; Farrar, Mark D.; Cruse-Sawyer, Janet E.; Holland, K. T.; Ingham, Eileen

doi:10.1046/j.1365-2133.2004.05762.x

Cited by 203 publications

(183 citation statements)

References 35 publications

Supporting

Mentioning

161

Contrasting

Unclassified

Order By: Relevance

“…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. 96 MUFA, mainly palmitic acid (C16:1) and oleic acid (C18:1), both of which are bactericidal against gram-positive organisms, 91 are produced by the sebaceous gland, as is sapienic acid, an important antimicrobial lipid.…”

Section: Resultsmentioning

confidence: 99%

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

Makrantonaki

Gancevičienė²,

Zouboulis³

2011

Dermato-Endocrinology

235

168

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

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

Makrantonaki

Gancevičienė²,

Zouboulis³

2011

Dermato-Endocrinology

235

168

View full text Add to dashboard Cite

“…The pathogenesis of this disease is complex, involving sebaceous gland hypertrophy, increased seborrhea with the presence of oxidized lipids, pilosebaceous duct hyperkeratinization, and colonization with Propionibacterium acnes, resulting in perifollicular inflammation (2,3). Among various mediators orchestrating the inflammatory response of the pilosebaceous unit in acne, several cytokines, including IL-1, IL-6, IL-8, and TNF-a, have been implicated (4)(5)(6)(7)(8). In particular, IL-1 appears to play a key role in the pathogenesis of acne.…”

mentioning

confidence: 99%

KdPT, a Tripeptide Derivative of α-Melanocyte–Stimulating Hormone, Suppresses IL-1β–Mediated Cytokine Expression and Signaling in Human Sebocytes

Mastrofrancesco

Kokot

Eberlé

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

Acne is the most common inflammatory skin disease in which IL-1 plays a central role. Although α-melanocyte–stimulating hormone has immunomodulatory effects, its usefulness as an anti-inflammatory agent in acne is hampered owing to its lipid- and pigment-inducing effects via activation of melanocortin receptors (MC-Rs). We used the immortalized human sebocyte line SZ95 as an in vitro model to investigate the anti-inflammatory potential of KdPT, a tripeptide derivative of the C-terminal end of α-melanocyte–stimulating hormone. KdPT potently suppressed IL-1β–induced IL-6 and IL-8 expression. Mechanistically, KdPT decreased IL-1β–mediated IκBα degradation, reduced nuclear accumulation of p65, and attenuated DNA binding of NF-κB. Moreover, KdPT reduced IL-1β–mediated generation of intracellular reactive oxygen species, which contributed to IL-1β–mediated cytokine induction. KdPT also reduced cell surface binding of fluorochrome-labeled IL-1β in SZ95 sebocytes. Analysis of the crystal structure of the complex between IL-1β/IL-1R type I (IL-1RI), followed by computer modeling of KdPT and subsequent modeling of the peptide receptor complex with the crystal structure of IL-1RI via manual docking, further predicted that the tripeptide, through several H-bonds and one hydrophobic bond, interacts with the IL-1RI. Importantly, KdPT did not bind to MC-1Rs, as demonstrated by blocking experiments with a peptide analog of Agouti signaling protein and by binding assays using MC-1R–expressing B16 melanoma cells. Accordingly, KdPT failed to induce melanogenesis. Our data demonstrate a promising anti-inflammatory potential of KdPT and point toward novel future directions in the treatment of acne—as well as of various other IL-1–mediated inflammatory diseases—with this small molecule.

show abstract

“…Although the correlation between the severity of acne and the number of P. acnes organisms is controversial (9), the first complete genome sequence of P. acnes raised the question of the pathogenic potential of this bacterium (1). This is further supported by recent studies showing that distinct P. acnes strains trigger the secretion of antimicrobial peptides and proinflammatory mediators from various cell types in vitro (4,6,7,14,15). Ever since the genetic and phylogenetic diversity of P. acnes was described (10-13), accumulating evidence has supported the challenging hypothesis that certain P. acnes strains may cause opportunistic infection, worsening acne lesions (5,14,15).…”

mentioning

confidence: 53%

Complete Genome Sequence of Propionibacterium acnesType IB Strain 6609

et al. 2011

View full text Add to dashboard Cite

Propionibacterium acnes is an anaerobic Gram-positive bacterium that forms part of the normal human cutaneous microbiota and is thought to play a central role in acne vulgaris, a chronic inflammatory disease of the pilosebaceous unit (I. Kurokawa et al., Exp. Dermatol. 18: 821-832, 2009). Here we present the whole genome sequence of P. acnes type IB strain 6609, which was recovered from a skin sample from a woman with no recorded acne history and is thus considered a nonpathogenic strain (I. Nagy, Microbes Infect. 8: 2195-2205, 2006).

show abstract

Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL

Abstract: Stimulation of cytokine production by P. acnes and P. acnes GroEL may be important in the pathogenesis of inflammatory acne vulgaris and may have wider implications for the immunomodulation of the human immune system by commensal skin microorganisms.

Cited by 203 publications

References 35 publications

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

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

KdPT, a Tripeptide Derivative of α-Melanocyte–Stimulating Hormone, Suppresses IL-1β–Mediated Cytokine Expression and Signaling in Human Sebocytes

Complete Genome Sequence of Propionibacterium acnesType IB Strain 6609

Contact Info

Product

Resources

About