IL-6 deficiency exacerbates skin inflammation in a murine model of irritant dermatitis

Lee, Eric G.; Mickle-Kawar, Bethany M.; Gallucci, Randle M.

doi:10.3109/1547691x.2012.707700

Cited by 37 publications

(37 citation statements)

References 40 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-6 also has anti-apoptotic activity in endothelial cells against H 2 O 2 -induced stress [67] and IR-induced death [68]. Additionally, IL-6 knockout mice die more readily from total body irradiation [69], mount an exaggerated inflammatory response to skin irritants [70] and exhibit slower wound re-epithelialization than wild-type mice [71]. These anti-apoptotic, pro-survival and pro-wound healing properties may explain why IL-6 levels in the VT-treated irradiated mice corresponded with better acute skin radiation damage outcomes in our experiments.…”

Section: Discussionmentioning

confidence: 99%

Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model

et al. 2014

View full text Add to dashboard Cite

BackgroundMost cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Acute skin damage from cancer radiotherapy diminishes patients’ quality of life, yet effective biological interventions for this damage are lacking. Protecting microvascular endothelial cells from irradiation-induced perturbations is emerging as a targeted damage-reduction strategy. Since Angiopoetin-1 signaling through the Tie2 receptor on endothelial cells opposes microvascular perturbations in other disease contexts, we used a preclinical Angiopoietin-1 mimic called Vasculotide to investigate its effect on skin radiation toxicity using a preclinical model.MethodsAthymic mice were treated intraperitoneally with saline or Vasculotide and their flank skin was irradiated with a single large dose of ionizing radiation. Acute cutaneous damage and wound healing were evaluated by clinical skin grading, histology and immunostaining. Diffuse reflectance optical spectroscopy, myeloperoxidase-dependent bioluminescence imaging of neutrophils and a serum cytokine array were used to assess inflammation. Microvascular endothelial cell response to radiation was tested with in vitro clonogenic and Matrigel tubule formation assays. Tumour xenograft growth delay experiments were also performed. Appreciable differences between treatment groups were assessed mainly using parametric and non-parametric statistical tests comparing areas under curves, followed by post-hoc comparisons.ResultsIn vivo, different schedules of Vasculotide treatment reduced the size of the irradiation-induced wound. Although skin damage scores remained similar on individual days, Vasculotide administered post irradiation resulted in less skin damage overall. Vasculotide alleviated irradiation-induced inflammation in the form of reduced levels of oxygenated hemoglobin, myeloperoxidase bioluminescence and chemokine MIP-2. Surprisingly, Vasculotide-treated animals also had higher microvascular endothelial cell density in wound granulation tissue. In vitro, Vasculotide enhanced the survival and function of irradiated endothelial cells.ConclusionsVasculotide administration reduces acute skin radiation damage in mice, and may do so by affecting several biological processes. This radiation protection approach may have clinical impact for cancer radiotherapy patients by reducing the severity of their acute skin radiation damage.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-614) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model

et al. 2014

View full text Add to dashboard Cite

show abstract

“…IL-6 promotes the pathogenesis of a variety of autoimmune or inflammatory disorders such as experimental autoimmune encephalomyelitis, rheumatoid arthritis and psoriasis [1, 4–6]. However, a growing number of reports have shown that IL-6 can also exert anti-inflammatory effects in a variety of autoimmune or inflammatory diseases [7–12]. IL-6 increases serum IL-1Rα, TNF receptor p55 and IL-10 levels in humans receiving IL-6 therapy and induces IL-1Rα production by human macrophages [13, 14].…”

Section: Introductionmentioning

confidence: 99%

“…IL-6 increases serum IL-1Rα, TNF receptor p55 and IL-10 levels in humans receiving IL-6 therapy and induces IL-1Rα production by human macrophages [13, 14]. IL-6 deficiency leads to exacerbated skin inflammation, accompanied by increased inflammatory mediators including TNF-α, IL-1β, in a mouse model of irritant dermatitis [7]. Furthermore, exogenous and endogenous IL-6 increases IL-1Rα in skin and serum in a mouse model of organ-specific autoimmune bullous dermatoses and plays a protective and anti-inflammatory role in this disease [12].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions

Zhou

Jin²,

Patel

et al. 2015

Cytokine

View full text Add to dashboard Cite

Interleukin (IL)-6 is a multi-functional cytokine that can either promote or suppress tissue inflammation depending on the specific disease context. IL-6 is elevated in the exocrine glands and serum of patients with Sjögren’s syndrome (SS), but the specific role of IL-6 in the pathogenesis of this disease has not been defined. In this study, we showed that IL-6 expression levels were increased with age in C56BL/6.NOD-Aec1Aec2 mice, a primary SS model, and higher than the control C57BL/6 mice. To assess the role of IL-6 during the immunological phase of SS development, a neutralizing anti-IL-6 antibody was administered into 16 week-old female C56BL/6.NOD-Aec1Aec2 mice, 3 times weekly for a consecutive 8 weeks. Neutralization of endogenous IL-6 throughout the immunological phase of SS development led to increased apoptosis, caspase-3 activation, leukocytic infiltration, and IFN-γ- and TNF-α production in the salivary gland. To further determine the effect of IL-6 on the apoptosis of exocrine gland cells, recombinant human IL-6 or the neutralizing anti-IL-6 antibody was injected into female C57BL/6 mice that received concurrent injection of anti-CD3 antibody to induce the apoptosis of exocrine glands. Neutralization of IL-6 enhanced, whereas administration of IL-6 inhibited apoptosis and caspase-3 activation in salivary and lacrimal glands in this model. The apoptosis-suppressing effect of IL-6 was associated with up-regulation of Bcl-xL and Mcl-1 in both glands. Moreover, IL-6 treatment induced activation of STAT3 and up-regulated Bcl-xL and Mcl-1 gene expression in a human salivary gland epithelial cell line. In conclusion, IL-6 inhibits the apoptosis of exocrine gland tissues and exerts a tissue-protective effect under inflammatory conditions including SS. These findings suggest the possibility of using this property of IL-6 to preserve exocrine gland tissue integrity and function under autoimmune and inflammatory conditions.

show abstract

“…IL-6 is a pro-inflammatory cytokine paradoxically associated with both skin healing and inflammation. It acts in an anti-inflammatory manner during irritant dermatitis (Lee et al, 2013). The immunohistochemical results demonstrated that the POD-loaded GA micelles could attenuate the expression of these two inflammatory cytokines (TNF-a and IL-6) in skin tissue, indicating that it had an anti-inflammatory effect.…”

Section: Discussionmentioning

confidence: 86%

Formulation and evaluation of novel glycyrrhizic acid micelles for transdermal delivery of podophyllotoxin

et al. 2016

View full text Add to dashboard Cite

Context: As the first-line agent for genital warts, podophyllotoxin (POD) could induce extensively skin burning, itching, and erythema. Meanwhile, as a common anti-inflammatory agent, glycyrrhizic acid (GA), also has amphipathic and solubilizing properties, indicating that it might be a promising drug carrier.Objective: The objective of this study is to formulate and characterize the POD-loaded GA micelles preparation and to evaluate its drug release characteristics and anti-inflammatory properties. Materials and methods:The novel micelles preparation was prepared by ultrasonic dispersion method and characterized using different scanning calorimetries, dynamic light scattering, and transmission electron microscopies. Subsequently, its encapsulation efficiency (EE), drugloading content (LC), in vitro skin permeation, in vivo drug retention, and distribution of POD were detected. The anti-inflammatory effect of the preparation was reflected by HE staining and immunohistochemistry in the rat skin.Results: The POD-loaded GA micelles formed spherical shapes (approximately 10 nm) with an EE of 78.53 ± 2.17% and a LC of 7.293 ± 0.42%. Meaningfully, unlike the extensive distribution of the POD tincture throughout the skin tissue, POD released from the POD-loaded GA micelles mainly located in the epidermis and could maintain steady skin retention for 12 h. Moreover, the POD-loaded GA micelles induced less leukocyte infiltration and inflammatory factors (IL-6 and TNF-a) expression when compared with the POD tincture. Discussion and conclusion: Our results suggested that the POD-loaded GA micelles could achieve a higher POD distribution in the epidermal layer as well as a lighter skin inflammation. This new POD delivery system might be a potential and promising candidate for genital warts and deserved further researches.

show abstract

IL-6 deficiency exacerbates skin inflammation in a murine model of irritant dermatitis

Cited by 37 publications

References 40 publications

Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model

Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model

Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions

Formulation and evaluation of novel glycyrrhizic acid micelles for transdermal delivery of podophyllotoxin

Contact Info

Product

Resources

About