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Staphylococcal superantigens stimulate immortalized human adipocytes to produce chemokines
Journal article   Open access   Peer reviewed

Staphylococcal superantigens stimulate immortalized human adipocytes to produce chemokines

Bao G Vu, Francoise A Gourronc, David A Bernlohr, Patrick M Schlievert and Aloysius J Klingelhutz
PloS one, Vol.8(10), pp.e77988-e77988
2013
DOI: 10.1371/journal.pone.0077988
PMCID: PMC3813495
PMID: 24205055
url
https://doi.org/10.1371/journal.pone.0077988View
Published (Version of record) Open Access

Abstract

Background Human adipocytes may have significant functions in wound healing and the development of diabetes through production of pro-inflammatory cytokines after stimulation by gram-negative bacterial endotoxin. Diabetic foot ulcers are most often associated with staphylococcal infections. Adipocyte responses in the area of the wound may play a role in persistence and pathology. We studied the effect of staphylococcal superantigens (SAgs) on immortalized human adipocytes, alone and in the presence of bacterial endotoxin or staphylococcal α-toxin. Methodology/Principal Findings Primary non-diabetic and diabetic human preadipocytes were immortalized by the reverse transcriptase component of telomerase (TERT) and the E6/E7 genes of human papillomavirus. The immortal cells were demonstrated to have properties of non-immortalized pre-adipocytes and could be differentiated into mature and functional adipocytes. Differentiated adipocytes exposed to staphylococcal SAgs produced robust levels of cytokines IL-6 and IL-8, but there were no significant differences in levels between the non-diabetic and diabetic cells. Cytokine production was increased by co-incubation of adipocytes with SAgs and endotoxin together. In contrast, α-toxin alone was cytotoxic at high concentrations, but, at sub-cytotoxic doses, did not stimulate production of IL-6 and IL-8. Conclusions/Significance Endotoxin has been proposed to contribute to diabetes through enhanced insulin resistance after chronic exposure and stimulation of adipocytes to produce cytokines. Our data indicate staphylococcal SAgs TSST-1 and SEB alone and in combination with bacterial endotoxin also stimulate adipocytes to produce cytokines and thus may contribute to the inflammatory response found in chronic diabetic ulcers and in the systemic inflammation that is associated with the development and persistence of diabetes. The immortal human pre-adipocytes reported here will be useful for studies to understand further the mechanism by which toxins are involved in wound healing and the development and clinical manifestations of obesity and diabetes.
 Bacterial Toxins - pharmacology Adipocytes - metabolism Humans Cells, Cultured Chemokines - metabolism Superantigens - pharmacology Adipocytes - drug effects Interleukin-8 - metabolism Enterotoxins - pharmacology Interleukin-6 - metabolism Wound Healing - drug effects

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