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Demodex mites modulate sebocyte immune reaction: Possible role in the pathogenesis of rosacea.

Br J Dermatol. 2018 Mar 12;:

Authors: Lacey N, Russell-Hallinan A, Zouboulis CC, Powell FC

Abstract
Rosacea is a common facial skin disorder affecting middle-aged adults. Its aetiology is unknown and pathogenesis uncertain. Activation of the host innate immune response has been identified as important. The Demodex mite population in the skin of these patients is significantly higher than in subjects with normal skin suggesting they may be of etiological importance in this disorder. Little is known of the role of these mites in human skin and their potential to interact with the host immune system has not been elucidated. Live Demodex mites were extracted from normal facial skin of control subjects and used in cell stimulation experiments with the immortalised SZ95 sebocyte line. Time and mite dose dependent experiments were performed. Direct Demodex effects and the effects of medium in which Demodex had been cultured were evaluated on the TLR-signalling pathway on both a gene and protein expression level. Mites modulated TLR signalling events on both mRNA and protein levels in SZ95 sebocytes. An initial trend towards down modulation of genes in this pathway was observed. A subsequent switch to positive gene up-regulation was recorded after 48 hours of co-culture. Demodex secreted bioactive molecules that affected TLR2 receptor expression by sebocytes. High numbers of Demodex induced pro-inflammatory cytokine secretion whereas lower numbers did not. Demodex mites have the capacity to modulate the TLR signalling pathway of an immortalised human sebocyte line. Mites have the capacity to secrete bioactive molecules that affect the immune reactivity of sebocytes. Increasing mite numbers influenced IL8 secretion by these cells. This article is protected by copyright. All rights reserved.

PMID: 29532463 [PubMed - as supplied by publisher]

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This statement gives some clearer understanding on the pathogenesis of demodectic rosacea: 

"High numbers of Demodex induced pro-inflammatory cytokine secretion whereas lower numbers did not. Demodex mites have the capacity to modulate the TLR signalling pathway of an immortalised human sebocyte line. Mites have the capacity to secrete bioactive molecules that affect the immune reactivity of sebocytes. Increasing mite numbers influenced IL8 secretion by these cells." 

Note these links: 
Demodectic Rosacea (Variant)
Demodex Density Count - What are the Numbers?

What is the Immortalized Human Sebaceous Gland Cell Line?
Answer: 

The human sebocyte culture model was first introduced in 1989. Cultured human sebocytes have been shown to preserve important sebocytic characteristics, although they undergo an incomplete terminal differentiation in vitro. Over the years, modifications of the technique have improved the culture of human sebocytes in vitro, but the primary cultured sebocytes can still be maintained for no more than six passages in vitro. The immortalized human sebaceous gland cell lines SZ95, SEB-1 and Seb-E6E7 have been developed in recent years, which make it possible to get a large number of sebocytes from the same donor culture. 
Dermatoendocrinol. 2009 Mar-Apr; 1(2): 92–95.
PMCID: PMC2835897
Culture of human sebocytes in vitro
Longqing Xia, Christos C Zouboulis, and Qiang Ju


Human facial sebaceous gland cells were transfected with a PBR-322-based plasmid containing the coding region for the Simian virus-40 large T antigen. The resulting proliferating cell cultures have been pas-saged over 50 times to date, have been cloned, and show no signs of senescence after 4&DF;1 2 y in vitro, whereas normal human sebocytes can only be grown for three to six passages.
Establishment and Characterization of an Immortalized Human Sebaceous Gland Cell Line (SZ95)
Christos C. Zouboulis, Holger Seltmann, Constantin E.Orfanos, Heidemarie Neitzel

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