Il-6 Expression by Oral Fibroblasts Is Regulated by Androgen

Parkar, MH; Tabona, P; Newman, H. N.; Olsen, I

doi:10.1006/cyto.1998.0336

Cited by 51 publications

(41 citation statements)

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“…Whereas both testosterone and DHT provoked a significant increase in macrophage IL-6 gene expression without greatly affecting TNF-␣ or TGF-␤1 mRNA levels, fibroblast IL-6 and TGF-␤1 mRNA levels and protein secretion were significantly reduced by treatment with testosterone or DHT and TNF-␣ mRNA expression decreased in response to exposure to DHT. These findings are partially corroborated by previous studies which demonstrated that DHT and testosterone inhibit IL-6 production by oral and gingival fibroblasts and that DHT but not testosterone stimulates secretion of IL-6 by Kupffer cells (Coletta et al, 2002;Gornstein et al, 1999;Parkar et al, 1998;Schneider et al, 2003). The failure of testosterone to enhance macrophage TNF-␣ gene expression contrasts sharply with the situation in mice, in which testosterone has been shown to increase both basal and LPS-induced mRNA levels (Ashcroft and Mills, 2002).…”

Section: Discussionsupporting

confidence: 80%

Androgens modulate the inflammatory response during acute wound healing

Gilliver¹,

Ashworth²,

Mills³

et al. 2006

Journal of Cell Science

128

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Impaired wound healing states in the elderly lead to substantial morbidity and mortality, and a cost to the health services of over $9 billion per annum. In addition to intrinsic ageing processes that per se cause delayed healing, studies have suggested marked differences in wound repair between the sexes. We have previously reported that, castration of male mice results in a striking acceleration of local cutaneous wound healing and dampens the associated inflammatory response. In this study, we report that systemic 5α-reductase inhibition, which blocks the conversion of testosterone to its more active metabolite 5α-dihydrotestosterone, mimics the effects of castration in a rat model of cutaneous wound healing. The mechanisms underlying the observed effects involve a direct, cell-specific upregulation of pro-inflammatory cytokine expression by macrophages, but not fibroblasts, in response to androgens. Androgens require the transforming growth factor β signalling intermediate Smad3 to be present in order to influence repair and local pro-inflammatory cytokine levels. That reducing 5α-dihydrotestosterone levels through 5α-reductase antagonism markedly accelerates healing suggests a specific target for future therapeutic intervention in impaired wound healing states in elderly males.

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Section: Discussionsupporting

confidence: 80%

Androgens modulate the inflammatory response during acute wound healing

Gilliver¹,

Ashworth²,

Mills³

et al. 2006

Journal of Cell Science

128

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“…This diVerent regulation of IL-6 levels in the two diVerent compartments is not surprising, considering that diVerent sources of salivary IL-6 were identiWed in the oral cavity: acinar cells of the salivary glands (Boumba et al 1995;Fox et al 1994;Yao et al 2005), oral epithelial cells (Formanek et al 1998(Formanek et al , 1999, periodontal ligament cells (Okada et al 1997;Yamamoto et al 2006), and gingival Wbroblasts (Okada et al 1997;Parkar et al 1998). All these sources are probably regulated by speciWc mechanisms which can diVer also with respect to those regulating muscle IL-6 production.…”

Section: Discussionmentioning

confidence: 98%

Influence of the sample collection method on salivary interleukin–6 levels in resting and post-exercise conditions

Minetto

Gazzoni²,

Lanfranco

et al. 2007

Eur J Appl Physiol

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Previous studies demonstrated that no significant relationships exist between salivary and serum IL-6 in resting conditions and following exercise and that appropriate saliva collection procedures allow to avoid analytical drawbacks. This investigation aimed to: (a) compare the effects of two methods of saliva collection on IL-6 assay; (b) search for correlation between salivary and serum IL-6 in resting and post-exercise conditions; (c) evaluate the IL-6 response to isometric contractions. Seventeen sedentary subjects and fifteen athletes underwent one blood and two salivary draws: saliva was collected chewing on cotton salivettes and using a plastic straw (SA method and ST method, respectively). Afterwards, the athletes only completed a fatiguing isometric exercise of the knee extensors and blood and saliva were sampled after the exercise. In the entire group (n=32), ST method produced higher IL-6 levels than SA method and serum sampling. The exercise elicited significant responses of lactate, serum IL-6, salivary IL-6 (by ST method): salivary IL-6 values using the ST collection method were higher at each sampling point than with the SA method. The correlation analyses applied to both resting levels in the entire group and absolute changes above baseline in the athlete group showed that: (1) no significant relationships exist between serum and salivary IL-6 levels; (2) the greater the salivary IL-6 measurement, the higher the resultant inaccuracy of the SA method; (3) significant correlations exist between isometric force and mechanical fatigue during exercise and peaks of lactate and serum IL-6. These data provided demonstration of a cotton-interference effect for the results of salivary IL-6 assay and confirmed the lack of significant correlation between salivary and serum IL-6 in resting and post-exercise conditions.

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“…Normal gingival tissue samples were obtained under the Eastman Dental Institute and Hospital Joint Ethics and Research Committee. Confluent cultures of gingival fibroblast (GF) cells were obtained by incubating biopsy samples of normal gingiva (NG) from five healthy individuals (three males and two females; age range 30 to 40 years, mean age 35 Ϯ 7.1), as previously described (18). The cells were detached from the monolayer by treating them with 0.25% trypsin in 1 mM ethylenediaminetetraacetic acid (EDTA) (Gibco Life Technologies Ltd., Paisley, UK), collected by centrifugation and serially passaged in 25 cm 2 tissue culture flasks (Falcon, Becton Dickinson Labware; Cowley, UK).…”

Section: Methodsmentioning

confidence: 99%