Involvement of Fas/FasL pathway in the murine model of atopic dermatitis

Bień, Karolina; Żmigrodzka, Magdalena; Orłowski, Piotr; Fruba, Aleksandra; Szymański, Łukasz; Stankiewicz, Wanda; Nowak, Zuzanna; Malewski, Tadeusz; Krzyżowska, Małgorzata

doi:10.1007/s00011-017-1049-z

Cited by 11 publications

(11 citation statements)

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“…The cell death machinery is activated by various apoptotic signals via the membrane (extrinsic) pathway. These apoptotic pathways are well studied in T cells, macrophages, and eosinophils, [20][21][22][23][24] like the pathway in which FasL activates Fas as a surface death receptor. One of the essential tools for the immune system to maintain immune homeostasis and to set up tolerance is to regulate cellular survival and death.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of Fas in Moderate/Severe and Mild Persistent Allergic Rhinitis and Its Correlation With Pathological Parameters

Pirayesh

Shahsavan

Samani

et al. 2019

Am J Rhinol�Allergy

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Background and Aims The roles of Fas in immune system are multifaceted, and the interaction between Fas receptor and Fas ligand is essential for maintaining the immune tolerance. We aimed to assess the level of the expression of Fas receptor on nasal inferior turbinate mucosa in patients with mild persistent allergic rhinitis (M PAR) and moderate to severe (M/S) PAR and determined the relationship between disease severity and production of Fas. Methods A total of 70 patients with M/S PAR, 70 patients with M PAR, and 70 healthy individuals were enrolled in this study. We obtained biopsies of nasal inferior turbinate mucosa from the participants. The expression of Fas mRNA was evaluated by real-time polymerase chain reaction. The presence and location of Fas were determined by immunohistochemistry. The number of eosinophils per field, blood eosinophils, total serum IgE levels, and specific serum IgE levels were measured. Clinical manifestations of patients were assessed by Total Nasal Syndrome Score (TNSS). Results The expression of Fas in patients with M/S PAR was decreased significantly compared to the control group and patients with M PAR. Local mucosal expression of Fas was correlated with specific IgE, nasal eosinophil count, and TNSS. Conclusion According to the results of this study, there might be a relationship between the expression of Fas receptor on nasal turbinate mucosa and the severity of persistent allergic rhinitis.

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Section: Discussionmentioning

confidence: 99%

Differential Expression of Fas in Moderate/Severe and Mild Persistent Allergic Rhinitis and Its Correlation With Pathological Parameters

Pirayesh

Shahsavan

Samani

et al. 2019

Am J Rhinol�Allergy

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“…For example, the PI3K/AKT signaling pathway is one of the major Src-activating pathways and may block the FAS-associated death domain protein to inhibit cellular apoptosis [ 24 , 25 ]. Thus, it is likely that IL-17 exerts its function through the FAS and FASL signaling pathways [ 26 , 27 ]. To date, little is known about the roles of IL-17 in LC, and the regulation of IL-17 in LC has not been fully investigated.…”

Section: Introductionmentioning

confidence: 99%

IL-17 Affects the Progression, Metastasis, and Recurrence of Laryngeal Cancer via the Inhibition of Apoptosis through Activation of the PI3K/AKT/FAS/FASL Pathways

Song

Yang

Zhang

et al. 2020

Journal of Immunology Research

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Background. Cytokines play important roles in the development and prognosis of laryngeal cancer (LC). Interleukin-17 (IL-17) from a distinct subset of CD4+ T cells may significantly induce cancer-elicited inflammation to prevent tumor immune surveillance. Methods. The expression levels of IL-17 were examined among 60 patients with LC. Immunofluorescence colocalization experiments were performed to verify the localization of IL-17 and FAS/FASL in Hep-2 and Tu212 cells. The role of IL-17 was determined using siRNA techniques in the LC cell line. Results. In the LC patients, cytokines were dysregulated in LC tissues compared with normal tissues. It was found that IL-17 was overexpressed in a cohort of 60 LC tumors paired with nontumor tissues. Moreover, high IL-17 expression was significantly associated with the advanced T category, the late clinical stage, differentiation, lymph node metastasis, and recurrence. In addition, the time course expression of FAS and FASL was observed after stimulation and treatment with the IL-17 stimulator. Finally, in vitro experiments demonstrated that IL-17 functioned as an oncogene by inhibiting the apoptosis of LC cells via the PI3K/AKT/FAS/FASL pathways. Conclusions. In summary, these findings demonstrated for the first time the role of IL-17 as a tumor promoter and a prometastatic factor in LC and indicated that IL-17 may have an oncogenic role and serve as a potential prognostic biomarker and therapeutic target in LC.

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“…Several factors play important role in the pathogenesis of AD which involve genetic, environmental, skin barrier, psychological and immunological factors. In various studies, Fas/FasL mediated keratinocyte apoptosis was demonstrated to be an important component of eczema and spongiosis in AD patients[ 1 ]. Epidermal keratinocytes express Fas and FasL proteins in low amounts [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Abnormal expression of lytically active FasL was found in inflammatory skin diseases such as toxic epidermal necrolysis, atopic dermatitis and allergic contact dermatitis [ 3 ]. As described in detail previously [ 1 ], scientific evidence indicates that Fas/FasL death receptors activate inflammatory or proliferative signaling via NF-κB or MAP kinase pathway [ 4 ]. MAPK pathway consists of three major components: proline-directed serine/threonine kinase known as the extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun NH 2 -terminal kinase (JNK).…”

Section: Introductionmentioning

confidence: 99%

Fas/FasL pathway and cytokines in keratinocytes in atopic dermatitis – Manipulation by the electromagnetic field

et al. 2018

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BackgroundAtopic dermatitis (AD) is one of the most frequent skin diseases. Changes of the keratinocytes functionality play a major role in the development of AD. For example, activation of the Fas (CD95)/FasL (CD178) pathway in AD does not lead to extensive apoptosis in skin. Binding of the Fas receptor to its protein ligand—FasL, which are present on the (AD)-modified keratinocytes, should result in the sequential induction of cell death, but there is no evidence of extensive apoptosis of these cells. This suggests that non-apoptotic mechanism of Fas/FasL pathway is commonly encountered, although not examined in the case of AD, phenomenon. An electromagnetic field, which was used to influence cultured cells in this study, can modulate proliferation, apoptosis, differentiation, and metabolism in various cells.ObjectiveHere, we evaluate the possibility to manipulate the immune activation of AD keratinocytes and their response to the electromagnetic field, which was not tested before.MethodsKeratinocytes isolated from the skin of healthy subjects (n = 20) and patients with atopic dermatitis (n = 20) as well as HaCaT and PCS-200-010 cell were exposed to the 900 MHz electromagnetic field for 60 minutes. Cytometric analysis of viability, Fas/FasL, p-ERK, p-p38 and p-JNK expression and Luminex analysis of cytokine concentration were performed in two-time points: 4 and 24 hours after the exposition.ResultsThis research has shown upregulated Fas, FasL, p-ERK, p-p38, and p-JNK expression along with increased cytokine secretion (IL-1β, IL-4, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-31 and TNFα) by keratinocytes derived from the skin of patients with the AD when compared with healthy control. Exposure of keratinocyte cultures obtained from AD patients to EMF resulted in a decrease of 1β, IL-4, IL-10, IL-12, I L-13, IL-17, IL-31 and TNFα levels. Keratinocytes derived from the skin of AD patients are characterized by elevated Fas and FasL expression when compared to healthy control.ConclusionApoptotic and nonapoptotic activation of the Fas/FasL-dependent signaling pathway may play a significant role in the pathogenesis of AD, by adjusting the local cytokine and chemokine environment at the site of inflammation. Moreover, the electromagnetic field exhibits strong immunomodulatory effects on AD-modified keratinocytes.

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Involvement of Fas/FasL pathway in the murine model of atopic dermatitis

Cited by 11 publications

References 37 publications

Differential Expression of Fas in Moderate/Severe and Mild Persistent Allergic Rhinitis and Its Correlation With Pathological Parameters

Differential Expression of Fas in Moderate/Severe and Mild Persistent Allergic Rhinitis and Its Correlation With Pathological Parameters

IL-17 Affects the Progression, Metastasis, and Recurrence of Laryngeal Cancer via the Inhibition of Apoptosis through Activation of the PI3K/AKT/FAS/FASL Pathways

Fas/FasL pathway and cytokines in keratinocytes in atopic dermatitis – Manipulation by the electromagnetic field

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