scholarly journals Interleukin-17A Drives IL-19 and IL-24 Expression in Skin Stromal Cells Regulating Keratinocyte Proliferation

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaofei Xu ◽  
Errol Prens ◽  
Edwin Florencia ◽  
Pieter Leenen ◽  
Luis Boon ◽  
...  
Keyword(s):  
Human Skin ◽  
Stromal Cells ◽  
Skin Inflammation ◽  
Skin Fibroblasts ◽  
Psoriatic Skin ◽  
Human Skin Fibroblast ◽  
Antibody Treatment ◽  
Keratinocyte Proliferation ◽  
Cellular Source ◽  
Enhanced Expression

IL-17A has been shown to be up-regulated in psoriasis lesions and is central to psoriasis pathogenesis. IL-19, along with other IL-20 subfamily cytokines such as IL-20 and IL-24, is induced by IL-17A and contributes especially to epidermal hyperplasia in psoriasis. However, the regulation, cellular sources of IL-19 and whether targeting of IL-17A by biologics influence IL-19 expression is not completely understood. To investigate the regulation of IL-19 by IL-17A in psoriasis, the imiquimod-induced psoriasis mouse (IMQ) model was used. Enhanced expression of IL-17A in the IMQ model was achieved by anti-IL-10 antibody treatment. Assessments of skin inflammation macroscopically, by histology and flow cytometry, all confirmed increased psoriatic symptoms. Interestingly, depletion of IL-10 markedly upregulated IL-23/IL-17 pathway related cytokines followed by a significant increase in IL-19 and IL-24. The up-regulation of IL-19 and IL-24, but not IL-17A, coincided with increased keratinocyte proliferation. To investigate the cellular source and effects of biologics on IL-19, human skin fibroblasts from healthy controls and psoriasis patients were cultured alone or co-cultured with activated memory CD4+ T cells. Besides IL-1β, IL-17A induced direct expression of IL-19 and IL-24 in skin fibroblasts and keratinocytes. Importantly, intrinsic higher expression of IL-19 in psoriatic skin fibroblasts was observed in comparison to healthy skin fibroblasts. Neutralization of IL-17A in the human skin fibroblast-T cell co-culture system significantly suppressed IL-19 and IL-24 expression. Together, our data show that IL-17A-induced IL-19 and IL-24 expression in skin stromal cells contribute to keratinocyte proliferation.

scholarly journals IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization

2016 ◽  
Vol 213 (10) ◽  
pp. 2147-2166 ◽  
Author(s):  
Juhan Yoon ◽  
Juan Manuel Leyva-Castillo ◽  
Guoxing Wang ◽  
Claire Galand ◽  
Michiko K. Oyoshi ◽  
...  
Keyword(s):  
T Cells ◽  
Human Skin ◽  
Cd4 T Cells ◽  
Mouse Skin ◽  
Skin Inflammation ◽  
Serum Levels ◽  
Skin Lesions ◽  
Tape Stripping ◽  
Keratinocyte Proliferation ◽  
Th22 Cells

Atopic dermatitis (AD) is a Th2-dominated inflammatory skin disease characterized by epidermal thickening. Serum levels of IL-22, a cytokine known to induce keratinocyte proliferation, are elevated in AD, and Th22 cells infiltrate AD skin lesions. We show that application of antigen to mouse skin subjected to tape stripping, a surrogate for scratching, induces an IL-22 response that drives epidermal hyperplasia and keratinocyte proliferation in a mouse model of skin inflammation that shares many features of AD. DC-derived IL-23 is known to act on CD4+ T cells to induce IL-22 production. However, the mechanisms that drive IL-23 production by skin DCs in response to cutaneous sensitization are not well understood. We demonstrate that IL-23 released by keratinocytes in response to endogenous TLR4 ligands causes skin DCs, which selectively express IL-23R, to up-regulate their endogenous IL-23 production and drive an IL-22 response in naive CD4+ T cells that mediates epidermal thickening. We also show that IL-23 is released in human skin after scratching and polarizes human skin DCs to drive an IL-22 response, supporting the utility of IL-23 and IL-22 blockade in AD.

scholarly journals Expression of Type XVI Collagen in Human Skin Fibroblasts: Enhanced Expression in Fibrotic Skin Diseases

1999 ◽  
Vol 113 (2) ◽  
pp. 246-250 ◽  
Author(s):  
Atsushi Akagi ◽  
Shingo Tajima ◽  
Yutaka Nagai ◽  
Akira Ishibashi ◽  
Noriko Yamaguchi
Keyword(s):  
Human Skin ◽  
Skin Diseases ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts ◽  
Enhanced Expression

scholarly journals Niosome Encapsulated Bromelain Reduced IL-6 and TNF-α in LPS Induced Human Skin Fibroblast Cell Line

2021 ◽  
Vol 2 (7) ◽  
pp. 01-10
Author(s):  
Siavash Hosseinpour Chermahini ◽  
Fadzilah Adibah Abdul Majid ◽  
Azila Abdul Aziz ◽  
Roya Anvari
Keyword(s):  
Cell Line ◽  
Human Skin ◽  
Skin Fibroblast ◽  
Skin Barrier ◽  
Fibroblast Cell ◽  
Skin Inflammation ◽  
Human Skin Fibroblast ◽  
Necrosis Factor Alpha ◽  
Tnf Α

The topical delivery of bromelain as an anti-inflammatory solution for skin inflammation has attracted the attention of researchers. Due to the skin barrier issue, a new method was designed for the effective delivery of specific doses of bromelain to the desired action sites. A niosome was selected as a novel and practical transdermal vehicle for the delivery of bromelain to inflamed sites. In this regard, a lipopolysaccharide (LPS)-induced human skin fibroblast (HSF1184) cell line was assembled in-vitro as a simulated model. The levels of interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α), the two immune-modulatory regulators of cell responses to inflammation, were measured to determine the response towards the niosome-encapsulated bromelain treatment. The results showed that the niosome-encapsulated bromelain significantly reduced the levels of IL-6 and TNF-α compared to the non-encapsulated bromelain, the vehicle (niosome) and the control.

scholarly journals Comparative analysis of bone marrow derived mesenchymal stromal cells, cardiac regional stem cells and human skin fibroblasts

2016 ◽  
Vol 19 (4-2) ◽  
pp. 12
Author(s):  
S. V. Pavlova ◽  
D. S. Sergeevichev ◽  
E. V. Chepeleva ◽  
V. S. Kozyreva ◽  
A. A. Malakhova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Comparative Analysis ◽  
Human Skin ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts

<p>Характерный маркер кардиальных стволовых клеток – тиразинкиназный рецептор c-kit. Клетки с фенотипом c-kit+ легко выделяются и культивируются in vitro. Однако истинным кардиомиогенным потенциалом обладают только кардиальные стволовые клетки, полученные из сердца постнатальных животных. Исследователи предполагают две популяции c-kit+ клеток в сердце различного происхождения в эмбриогенезе. Клетки c-kit+, способные дифференцироваться в кардиомиоциты, происходят из клеток первичного кардиального поля и исчезают вскоре после рождения, а те, что имеют проэпикардиальное происхождение, экспрессируют мезенхимальные маркеры и способны к дифференцировке в эндотелиальном, муральном и фибробластном направлениях. Ранее мы описали c-kit+ клетки, выделенные из фрагментов ушка правого предсердия, и исследовали их ангиогенный потенциал in vitro. В этом исследовании мы сравнили поверхностные маркеры мезенхимальных стволовых клеток костного мозга, кардиальных стволовых клеток и фибробластов кожи человека методом проточной цитометрии и полимеразной цепной реакции с обратной транскрипцией. Показали, что культура кардиальных стволовых клеток человека, полученная в результате магнитного сортинга с помощью антител на c-kit-рецептор является гетерогенной. В ней присутствуют клетки, несущие характерный набор поверхностных маркеров мезенхимальных стволовых клеток костного мозга, эндотелиальных и муральных клеток. Иммунофенотип фибробластов кожи также представлен характерным набором маркеров мезенхимальных стволовых клеток, за исключением дополнительного маркера CD10, соответствующего эластазе, нейтральной пептидазе. Кроме того, фибробласты кожи дифференцируются в остеогенном и адипогенном направлениях при использовании индукционных сред. Таким образом, фибробласты кожи человека, полученные согласно стандартным протоколам, являются мезенхимальными стволовыми клетками кожи. В соответствии с иммунофенотипом мезенхимальные стволовые клетки костного мозга, кардиальные стволовые клетки и фибробласты кожи экспрессируют гены паракринных факторов HGF, VEGF, PDGFb, ANG1, ANG2, IGF1, TGFb, обладающих кардиопротекторным и ангиогенным эффектами.</p>

scholarly journals Inventory of human skin fibroblast proteoglycans. Identification of multiple heparan and chondroitin/dermatan sulphate proteoglycans

1990 ◽  
Vol 265 (1) ◽  
pp. 289-300 ◽  
Author(s):  
A Schmidtchen ◽  
I Carlstedt ◽  
A Malmström ◽  
L Å Fransson
Keyword(s):  
Human Skin ◽  
Culture Medium ◽  
Heparan Sulphate ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblast ◽  
Heparan Sulphate Proteoglycan ◽  
Dermatan Sulphate ◽  
The Core ◽  
Sulphate Proteoglycan ◽  
Core Proteins

Heparan sulphate and chondroitin/dermatan sulphate proteoglycans of human skin fibroblasts were isolated and separated after metabolic labelling for 48 h with 35SO4(2-) and/or [3H]leucine. The proteoglycans were obtained from the culture medium, from a detergent extract of the cells and from the remaining ‘matrix’, and purified by using density-gradient centrifugation, gel and ion-exchange chromatography. The core proteins of the various proteoglycans were identified by electrophoresis in SDS after enzymic removal of the glycosaminoglycan side chains. Skin fibroblasts produce a number of heparan sulphate proteoglycans, with core proteins of apparent molecular masses 350, 250, 130, 90, 70, 45 and possibly 35 kDa. The major proteoglycan is that with the largest core, and it is principally located in the matrix. A novel proteoglycan with a 250 kDa core is almost entirely secreted or shed into the culture medium. Two exclusively cell-associated proteoglycans with 90 kDa core proteins, one with heparan sulphate and another novel one with chondroitin/dermatan sulphate, were also identified. The heparan sulphate proteoglycan with the 70 kDa core was found both in the cell layer and in the medium. In a previous study [Fransson, Carlstedt, Cöster & Malmström (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 5657-5661] it was suggested that skin fibroblasts produce a proteoglycan form of the transferrin receptor. However, the core protein of the major heparan sulphate proteoglycan now purified does not resemble this receptor, nor does it bind transferrin. The principal secreted proteoglycans are the previously described large chondroitin sulphate proteoglycan (PG-L) and the small dermatan sulphate proteoglycans (PG-S1 and PG-S2).

scholarly journals EGFR-mediated expression of aquaporin-3 is involved in human skin fibroblast migration

2006 ◽  
Vol 400 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Cong Cao ◽  
Yun Sun ◽  
Sarah Healey ◽  
Zhigang Bi ◽  
Gang Hu ◽  
...  
Keyword(s):  
Cell Migration ◽  
Human Skin ◽  
Skin Fibroblast ◽  
Kinase Inhibitor ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblast ◽  
Human Skin Fibroblasts ◽  
Aquaporin 3 ◽  
Fibroblast Migration ◽  
Normal Wound Healing

AQP3 (aquaporin-3), known as an integral membrane channel in epidermal keratinocytes, facilitates water and glycerol movement into and out of the skin. Here, we demonstrate that AQP3 is also expressed in cultured human skin fibroblasts, which under normal wound healing processes migrate from surrounding tissues to close the wound. EGF (epidermal growth factor), which induced fibroblast migration, also induced AQP3 expression in a time- and dose-dependent manner. CuSO4 and NiCl2, previously known as AQP3 water transport inhibitors, as well as two other bivalent heavy metals Mn2+ and Co2+, inhibited EGF-induced cell migration in human skin fibroblasts. AQP3 knockdown by small interfering RNA inhibited EGF-induced AQP3 expression and cell migration. Furthermore, an EGFR (EGF receptor) kinase inhibitor, PD153035, blocked EGF-induced AQP3 expression and cell migration. MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase]/ERK inhibitor U0126 and PI3K (phosphoinositide 3-kinase) inhibitor LY294002 also inhibited EGF-induced AQP3 expression and cell migration. Collectively, our findings show for the first time that AQP3 is expressed in human skin fibroblasts and that EGF induces AQP3 expression via EGFR, PI3K and ERK signal transduction pathways. We have provided evidence for a novel role of AQP3 in human skin fibroblast cell migration, which occurs during normal wound healing.

scholarly journals Regenerative effects of spring water-derived bacterial lysates on human skin fibroblast in in vitro culture: preliminary results

2019 ◽  
Vol 47 (11) ◽  
pp. 5777-5786 ◽  
Author(s):  
Giovanni Nicoletti ◽  
Marco Saler ◽  
Marco Mario Tresoldi ◽  
Angela Faga ◽  
Mattia Benedet ◽  
...  
Keyword(s):  
In Vitro Culture ◽  
Human Skin ◽  
Spring Water ◽  
Skin Fibroblasts ◽  
The Other ◽  
Human Skin Fibroblast ◽  
Human Skin Fibroblasts ◽  
Experimental Conditions ◽  
Bacterial Lysates

Objective: Previous studies have shown regenerative power of the skin with Comano (Trento, Italy) spring water and resident non-pathogenic microflora. This study investigated the action of bacterial lysates that were isolated from Comano spring water on in vitro culture of human skin fibroblasts. Methods: For this study, we selected the following four bacterial lysates: L1 (closest relative: Rudaea cellulosilytica), L2 (closest relative: Mesorhizobium erdmanii), L3 (closest relative: Herbiconiux ginsengi), and L4 (closest relative: Fictibacillus phosphorivorans). Human fibroblasts were cultured under Dulbecco’s modified Eagle’s medium (DMEM) with bacterial lysates added or DMEM (controls). Cell proliferation was evaluated by spectrophotometric absorbance analysis after the XTT-Microculture Tetrazolium Assay. Results: At 24 hours, cultures with L2, L3, and L4 showed a higher absorbance compared with controls. At 48 hours, cultures with L1, L2, and L3 showed slightly lower absorbance compared with controls, and culture with L4 showed a higher absorbance than in the other experimental conditions. At 72 hours, absorbance was lower in cultures with L1, L2, and L3 than in controls, and absorbance was higher in culture with L4 than in the other experimental conditions. Conclusions: Our study indicates a favorable action of Comano spring water microbiota on proliferation of human skin fibroblasts.

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