interleukin-8 and Cicatrix--Hypertrophic

Treatment of hypertrophic scars can be difficult for both patients and physicians. Silicone-containing gel dressings have been reported to be an effective alternative treatment for hypertrophic scars, yet the mechanism of action of these dressings is unknown.. To determine whether silicone is an essential factor in the treatment of hypertrophic scars and investigate the effects of occlusive dressing therapy on the expression of key wound healing mediators.. A pilot paired comparison, nonrandomized study was conducted comparing a silicone gel sheeting (Silastic [SGS]) with a hydrogel dressing (ClearSite). The effects of the dressings were compared side by side in the treatment of 15 hypertrophic scars at both the clinical and molecular levels through the use of reverse transcriptase/polymerase chain reaction to evaluate effects on the expression of interleukin 8 (IL-8), basic fibroblast growth factor (bFGF), granulocyte-macrophage colony-stimulating factor (GMCSF), epidermal growth factor (EGF), transforming growth factor beta (TGF-beta), and fibronectin.. Comparable clinical improvement of the hypertrophic scars was obtained with both dressings. Treatment of hypertrophic scars resulted in increased mean levels of IL-8, bFGF, and GMCSF mRNA; while mean TGF beta and fibronectin mRNAs decreased after treatment with both dressings. Comparison between the two dressings revealed significant changes in IL-8 and fibronectin mRNA levels after treatment with ClearSite, while only fibronectin changes were significant after treatment with SGS with respect to normal skin. Only ClearSite induced significant changes in IL-8 and bFGF levels when untreated scars were compared with posttreatment lesions, suggesting that the hydrogel augments collagenolysis via promotion of inflammation.. This study demonstrates that silicone is not a necessary component of occlusive dressings in the treatment of hypertrophic scars. The pathogenesis of hypertrophic scars is further elucidated by demonstrating that there is molecular evidence for extensive connective tissue remodeling occurring during occlusive dressing therapy.

Topics: Adult; Aged; Cicatrix, Hypertrophic; Collagen; Connective Tissue; Cytokines; Epidermal Growth Factor; Fibroblast Growth Factor 2; Fibronectins; Gels; Gene Expression Regulation; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Inflammation; Interleukin-8; Middle Aged; Occlusive Dressings; Pilot Projects; Polyethylene Glycols; Polymerase Chain Reaction; Polyurethanes; RNA, Messenger; Silicone Elastomers; Silicones; Skin; Transforming Growth Factor beta; Wound Healing

The mechanisms of hypertrophic scar formation and its tissue inflammation remain unknown.. We collected 33 hypertrophic scar (HS) and 36 normal skin (NS) tissues, and detected the tissue inflammation and bacteria using HE staining, Gram staining, and transmission electronic microscopy (TEM),. HE staining showed that a dramatically increased number of inflammatory cells accumulated in HS compared with NS, and an enhanced number of bacteria colonies was found in HS by Gram staining, even individual bacteria could be clearly observed by TEM.. Microbiome dysbiosis, dominated by

Topics: Cicatrix, Hypertrophic; Dysbiosis; Humans; Inflammation; Interleukin-6; Interleukin-8; Methicillin-Resistant Staphylococcus aureus; RNA, Ribosomal, 16S; Staphylococcus aureus; Tumor Necrosis Factor-alpha

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP-1, IL-8, IL-18 and IL-23 levels have a strong correlation with HS (P < .010-0.004; AUC = 0.790-0.883). Notably, combinations of two or three cytokines (TNF-a, MCP-1 and IL-23; AUC: 0.942, Nagelkerke R

Topics: Adult; Area Under Curve; Case-Control Studies; Chemokine CCL2; Cicatrix, Hypertrophic; Cytokines; Humans; Interleukin-18; Interleukin-23; Interleukin-8; Leukocytes, Mononuclear; Middle Aged; Patch Tests; Predictive Value of Tests; Prognosis; Prospective Studies; ROC Curve; Skin Irritancy Tests; Sodium Dodecyl Sulfate; Tumor Necrosis Factor-alpha

To evaluate the therapeutic effect of micro-plasma radio frequency on hypertrophic scars in rabbit ears to provide an experimental basis and theoretical foundation for the treatment of hypertrophic scars. Hypertrophic scars were established on the ventral surface of the ears of six New Zealand white rabbits. Left and right ears were randomly divided into two groups: experimental group treated with micro-plasma radio frequency and control group with no treatment. H&E staining and CD34 labeling of microvessels were performed to analyze ear specimens, and immunohistochemical staining was conducted to detect IL-8 and MCP-1 in the scars. Compared with the control group, scar tissue in the experimental group was improved by color and texture. H&E-stained collagen fiber bundles were more organized after treatment as assessed by optical microscopy. The number of microvessels in the experimental group was decreased compared with that in the control group. Microvascular density was significantly reduced in the experimental group compared with the control group (27.16 ± 5.64 and 48.75 ± 8.25 mm

Topics: Animals; Chemokine CCL2; Cicatrix, Hypertrophic; Ear; Female; Interleukin-8; Microvessels; Rabbits; Radiofrequency Therapy

Keloid scars are often described as having an actively growing peripheral margin with a regressing centre. The aim of this study was to examine the possible heterogeneity within keloids and the involvement of different regions within and around keloid scars in the pathogenesis, using an in vitro keloid scar model. In vitro skin models were constructed from keratinocytes and fibroblasts from normal skin and different regions within and around keloid scars: periphery, centre, and (adjacent) surrounding-normal-skin regions. Additionally, fibroblasts were isolated from the superficial-central and deep-central regions of the keloid and combined with central keratinocytes. All keloid regions showed increased contraction compared to normal skin models, particularly in central regions. Myofibroblasts were present in all keloid regions but were more abundant in models containing central-deep keloid fibroblasts. Secretion of anti-fibrotic HGF and extracellular matrix collagen IV gene expression was reduced in the central deep keloid compared to normal skin. No significant differences between peripheral and central regions within keloids were observed for inflammatory cytokine CCL20, CCL27, CXCL8, IL-6 and IL-18 secretion. Parameters for surrounding-normal-skin showed similarities to both non-lesional normal skin and keloids. In conclusion, a simple but elegant method of culturing keloid-derived keratinocytes and fibroblasts in an organotypic 3D scar model was developed, for the dual purpose of studying the underlying pathology and ultimately testing new therapeutics. In this study, these tissue engineered scar models show that the central keloid region shows a more aggressive keloid scar phenotype than the periphery and that the surrounding-normal-skin also shares certain abnormalities characteristic for keloids.

Topics: Cell Proliferation; Chemokine CCL20; Chemokine CCL27; Child; Child, Preschool; Cicatrix, Hypertrophic; Collagen; Female; Fibroblasts; Hepatocyte Growth Factor; Humans; Infant; Interleukin-18; Interleukin-6; Interleukin-8; Keloid; Keratinocytes; Male; Myofibroblasts; Skin

Adverse hypertrophic scars can form after healing of full-thickness skin wounds. Currently, reliable animal and in vitro models to identify and test novel scar reducing therapeutics are scarce. Here we describe the development and validation of a tissue-engineered human hypertrophic scar (HTscar) model based on reconstructed epidermis on a dermal matrix containing adipose derived mesenchymal stem cells (ASC). Although obtained from normal, healthy skin, ASC, in contrast to dermal mesenchymal cells, were found to facilitate HTscar formation. Quantifiable HTscar parameters were identified: contraction; thickness of dermis, collagen-1 secretion, epidermal outgrowth, epidermal thickness, and cytokine secretion (IL-6, CXCL8). The model was validated with therapeutics currently used for treating scars (5-fluorouracil, triamcinolon) and a therapeutic known to be unsuccessful in scar reduction (1,25-dihydroxyvitamin-D3). Furthermore, it was shown that atorvastatin, but not retinoic-acid, may provide a suitable alternative for scar treatment. Each therapeutic selectively affected a different combination of parameters, suggesting combined therapy may be most beneficial. This animal-free hypertrophic scar model may provide an alternative model for mechanistic studies as well as a novel in vitro means to test anti-scar therapeutics, thereby reducing the use of animals.

Topics: Animal Testing Alternatives; Atorvastatin; Cell Proliferation; Cicatrix, Hypertrophic; Gene Expression Regulation; Hazardous Substances; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Interleukin-8; Mesenchymal Stem Cells; Models, Biological; Pyrroles; Reproducibility of Results; Skin; Tissue Engineering

Hypertrophic scar (HTS), a fibroproliferative disorder (FPD), complicates burn wound healing. Although the pathogenesis is not understood, prolonged inflammation is a known contributing factor. Emerging evidence suggests that fibroblasts regulate immune/inflammatory responses through toll-like receptor 4 (TLR4) activated by lipopolysaccharide (LPS) through adaptor molecules, leading to nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinases activation, cytokine gene transcription and co-stimulatory molecule expression resulting in inflammation. This study explored the possible role of TLR4 in HTS formation. Paired normal and HTS tissue from burn patients was collected and dermal fibroblasts isolated and cultured. Immunohistochemical analysis of tissues demonstrated increased TLR4 staining in HTS tissue. Quantitative RT-PCR of three pairs of fibroblasts demonstrated mRNA levels for TLR4 and its legend myeloid differentiation factor 88 (MyD88) in HTS fibroblasts were increased significantly compared with normal fibroblasts. Flow cytometry showed increased TLR4 expression in HTS fibroblasts compared with normal. ELISA demonstrated protein levels for prostaglandin E2, interleukin (IL)-6, IL-8 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in HTS fibroblasts compared to normal. When paired normal and HTS fibroblasts were stimulated with LPS, significant increases in mRNA and protein levels for MyD88, IL-6, IL-8, and MCP-1 were detected. However, when transfected with MyD88 small interfering RNA (siRNA), then stimulated with LPS, a significant decrease in mRNA and protein levels for these molecules compared to only LPS-stimulated fibroblasts was detected. In comparison, a scramble siRNA transfection did not affect mRNA or protein levels for these molecules. Results demonstrate LPS stimulates proinflammatory cytokine expression in dermal fibroblasts and MyD88 siRNA eliminates the expression. Therefore, controlling inflammation and manipulating TLR signaling in skin cells may result in novel treatment strategies for HTS and other FPD.

Topics: Adolescent; Adult; Burns; Cells, Cultured; Chemokine CCL2; Child, Preschool; Cicatrix, Hypertrophic; Dinoprostone; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; Flow Cytometry; Humans; Immunohistochemistry; Inflammation Mediators; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Myeloid Differentiation Factor 88; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA, Messenger; Skin; Toll-Like Receptor 4; Transfection

To investigate the role of prostaglandin (PG) E1 in preventing scar formation as well as that of the related cytokines, we culture fibroblasts from hypertrophic scar tissue (SDF) and normal dermis (NDF) collected from patients with scar contracture. We have compared the type I collagen synthesis, type I collagenase activity, and the production of interleukin (IL)-6, IL-8 and transforming growth factor (TGF)-beta(1) in two types of cultured fibroblasts before and after addition of PGE1. Our results demonstrated that levels of type I collagen and TGF-beta(1) production were higher and that type I collagenase activity and IL-8 production were significantly lower in the culture supernatants of SDF. There was no significance difference in IL-6 production between SDF and NDF culture supernatants. On the other hand, PGE1 significantly increased type I collagenase activity and IL-8 production in the SDF culture supernatants and it increased IL-6 and TGF-beta(1) production in both types of fibroblasts. However, there was no effect on synthesis of type I collagen in either group. To further investigate the role of TGF-beta(1) in NDF and SDF, exogenous recombinant human (rh) TGF-beta(1) was added. In NDF group, rhTGF-beta(1) induced a decrease in the type I collagenase/type I collagen ratio, while rhTGF-beta(1) had no effect on the same ratio in the SDF group. These results suggest that PGE1 may have a role in the prevention of hypertrophic scar by increasing the activity of type I collagenase.

Topics: Adolescent; Adult; Alprostadil; C-Peptide; Cells, Cultured; Cicatrix, Hypertrophic; Collagenases; Cytokines; Extracellular Matrix; Female; Fibroblasts; Humans; Interleukin-6; Interleukin-8; Male; Recombinant Proteins; Skin; Transforming Growth Factor beta

The effects of prostaglandin (PG) I1 analog, SM-10906 (SM-6) and PGE1 on extracellular matrix formation and the release of cytokines by cultured normal human dermal fibroblasts (NDF) and hypertrophic scar fibroblasts (HSF) were compared in order to evaluate the clinical efficacy of PGs in preventing scar formation. In the present study, we measured type I collagen synthesis, collagenase activity, production of interleukin (IL)-6, IL-8, and transforming growth factor (TGF)-beta 1 and levels of adenosine 3,5-cyclic monophosphate (cAMP) in NDF and HSF cultured with or without PGs. The results demonstrated that HSF culture supernatants has a significantly higher level of type I collagen and TGF-beta 1 than those of NDF. However, the levels of collagenase activity and IL-8 in HSF were significantly lower in comparison to that of NDF. There was no substantial difference in IL-6 production between two types of culture cells. On the other hand, PGE1 and SM-6 significantly enhanced collagenase activity and raised the collagenase/type I collagen ratio in the HSF supernatants. In addition, both PGE1 and SM-6 increased production of TGF-beta 1, IL-8 and IL-6 and levels of cAMP in both cell types. However, they had no effect on the type I collagen synthesis of either types. These results suggest that, the stable PGI1 analog, SM-6, similarly acts as PGE1 in HSF by increasing the activity of collagenase.

Topics: Adolescent; Adult; alpha-2-Antiplasmin; Alprostadil; Antifibrinolytic Agents; C-Peptide; Cicatrix, Hypertrophic; Collagen; Collagenases; Cyclic AMP; Cytokines; Dose-Response Relationship, Drug; Epoprostenol; Extracellular Matrix; Female; Fibrinolysin; Fibroblasts; Humans; Interleukin-6; Interleukin-8; Male; Platelet Aggregation Inhibitors; Transforming Growth Factor beta