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1.
Chanat Kumtornrut Takeshi Yamauchi Saaya Koike Setsuya Aiba Kenshi Yamasaki 《Journal of dermatological science》2019,93(3):150-158
Background
The main pathogenesis of acne vulgaris is increase in sebum production and abnormal keratinization of the hair infundibulum. The androgens are involved in acne pathogenesis by modulating sebaceous glands to enhance sebum production. However, the molecular mechanisms of abnormal keratinization of the hair infundibulum are not fully elucidated.Objective
We hypothesized that the androgens affect the dermal fibroblasts, another androgen receptor-positive cells in the skin, resulting in abnormal keratinization through keratinocyte-fibroblast interaction.Methods
We investigated effects of androgens and estrogens on growth factors expressions by RT-PCR and western blot analysis in human fibroblast (hFB), human keratinocyte (hKC), and fibroblast-keratinocyte co-culture. In vivo, we examined the growth factor expression in acne lesions compared to normal hair follicles by laser-assisted confocal microscope.Results
In vitro, androgens but not estrogens significantly increased amphiregulin (AREG), epiregulin (EREG), fibroblast growth factor (FGF) 10, and insulin-like growth factor binding protein (IGFBP) 5 mRNA and protein expressions in human fibroblasts but not in keratinocytes. In vivo, AREG, EREG, FGF10, and IGFBP5 were more abundant in acne lesion compared to normal facial skin. FGF10 suppressed cytokeratin 1 and cytokeratin 10 expression in hKC, which was along with the decreased ratio of cytokeratin 10 against cytokeratin 14 in acne lesions compared to normal facial skin. Also, DHT suppressed cytokeratin 1 and cytokeratin 10, in fibroblast-keratinocyte co-culture similarly to the effect of FGF10 to hKC.Conclusion
These observations suggested that androgens enhance growth factors production from dermal fibroblasts, and growth factors from fibroblasts alter keratinocyte differentiation in acne lesion. 相似文献2.
Hsiao-Chi Lai Chang-Shen Lin Ching-Shuang Wu Cheng-Che E. Lan 《Journal of dermatological science》2019,93(2):116-122
Background
Ultraviolet B (UVB) is commonly used for treating dermatologic conditions. Recently, high irradiance UVB (HIUVB) has been suggested to be more effective for treating skin conditions as compared to its low irradiance (LI) counterpart. The biological impact of UVB radiation emitted at different irradiance on cutaneous immunity remains obscure.Objective
This study aimed to explore the impacts of UVB radiation administered at equivalent fluence (mJ/cm2) but different irradiance (mW/cm2) on cutaneous immune response.Methods
Cultured bone marrow derived dendritic cell (BMDC) were treated with equivalent fluence of UVB radiation with HIUVB or LIUVB. The phenotypic and functional alterations of BMDCs were documented. Animal models were used to validate the in vitro results in vivo and explore the mechanisms involved.Results
After equivalent fluence of UVB radiation, the HIUVB treated BMDC showed significantly lower MHCII and CD86 expressions, reduced capacity to stimulate T cell proliferation, and enhanced activation of aryl hydrocarbon receptor (AhR)-activated genes as compared to control while their LIUVB treated counterpart showed no significant change. Using animal model, the HIUVB induced significantly higher immune suppressive effect in mice as compared to their LIUVB counterpart after equivalent fluence of UVB treatment. The superior immune suppressive effect of HIUVB over LIUVB radiation was not observed when similar experiments were performed using AhR-deficient mice.Conclusion
We propose irradiance played an important role modulating UVB-induced cutaneous immune suppression. Future works on UVB phototherapy, both clinical and research, should incorporate this important parameter into consideration. 相似文献3.
4.
Ryosuke Saigusa Yoshihide Asano Takashi Yamashita Takehiro Takahashi Kouki Nakamura Shunsuke Miura Yohei Ichimura Tetsuo Toyama Takashi Taniguchi Hayakazu Sumida Zenshiro Tamaki Miki Miyazaki Ayumi Yoshizaki Shinichi Sato 《Journal of dermatological science》2018,89(3):282-289
Background
Scleroderma is a chronic disease of unknown etiology characterized by skin fibrosis and is divided into two clinical entities: systemic sclerosis (SSc) and localized scleroderma (LSc). In general, LSc is rarely complicated with SSc, but a certain portion of SSc patients manifests bilateral symmetric LSc-like lesions on the trunk and extremities.Objective
We investigated SSc patients with LSc-like lesions to clarify the underlying pathophysiology.Methods
Nine SSc cases complicated with LSc-like lesions were clinically and histologically characterized.Results
SSc patients with LSc-like lesions exhibited multiple progressive hyper- and/or hypo-pigmented plaques with mild sclerosis symmetrically distributed on the trunk and extremities, especially abdominal region. In histological assessment, epidermal IL-1α expression was elevated in both forearms and LSc-like lesions of these patients to a greater extent than in forearms of control patients (SSc patients without LSc-like lesions). Of note, the infiltration and degranulation of mast cells were evident throughout the dermis of LSc-like lesions, while detectable to a lesser extent in forearms of SSc patients with LSc-like lesions and control patients.Conclusion
The epidermis of SSc patients with LSc-like lesions seems to possess an inflammatory phenotype, leading to the activation of mast cells in the dermis of mechanically stressed skin. Köbner phenomenon may be involved in the induction of LSc-like lesions in a certain subset of SSc. 相似文献5.
Mai Kanemaru Jun Asai Jun-ichiro Jo Takahiro Arita Minako Kawai-Ohnishi Miho Tsutsumi Makoto Wada Yasuhiko Tabata Norito Katoh 《Journal of dermatological science》2019,93(1):41-49
Background
Nanoparticle-loaded delivery systems have attracted much attention recently. Poly(lactic-co-glycolic acid) (PLGA) is one of the most successful biodegradable polymers for biomedical applications. There are only a few studies on the treatment of dermal fibrosis with sustained-release drugs. Peroxisome proliferator-activated receptor-γ (PPAR-γ) plays an important role in endogenous anti-fibrotic defense mechanisms. Recent studies have suggested that pioglitazone, a synthetic PPAR-γ activator, has effects beyond reducing blood sugar and it can reduce fibrosis and inflammation when used systemically.Objective
We aimed to assess the effects of local injections of pioglitazone-loaded PLGA nanoparticles (PGN-NP) on an experimental sclerosis and to demonstrate the in vivo pharmacokinetics of subcutaneously administered PLGA nanoparticles.Methods
Locally injectable PGN-NP were prepared and subcutaneously administered to bleomycin (BLM)-induced scleroderma model mice. The effect of pioglitazone was also evaluated with cultured fibroblasts. Coumarin-6-loaded fluorescent PLGA nanoparticles (FL-NP) and silicon naphthalocyanine-loaded near-infrared PLGA nanoparticles (NIR-NP) were used to demonstrate in vitro cellular uptake by cultured fibroblasts and the in vivo pharmacokinetics of subcutaneously administered nanoparticles.Results
Weekly subcutaneous injections of PGN-NP attenuated skin fibrosis in BLM-induced scleroderma model mice. Pioglitazone significantly suppressed migration ability and TGF-β-mediated myofibroblast differentiation in cultured fibroblasts. FL-NP were internalized into cultured fibroblasts within 60?min, and PGN-NP-primed fibroblasts expressed anti-fibrotic phenotypes. Subcutaneously injected NIR-NP remained in the vicinity of the injection site more than non-particulate silicon naphthalocyanine.Conclusion
These results provide a basis for the development of new treatments for dermal fibrosis and a better understanding of the potential of PLGA nanoparticles in dermatology. 相似文献6.
Yu-Jing Zhang Yang Han Yu-Zhe Sun Hang-Hang Jiang Min Liu Rui-Qun Qi Xing-Hua Gao 《Journal of dermatological science》2019,93(3):168-175
Background
Malassezia is one of the commensal microorganisms colonized on human skin and has been shown to be related to several inflammatory cutaneous disorders. Previous studies indicated that Malassezia. sympodialis (M. sympodialis) can produce extracellular vesicles, however, the immunoregulatory function of Malassezia extracellular vesicles on keratinocytes has not been studied.Objective
To investigate the extracellular vesicular production capability of Malassezia. furfur (M. furfur) and examine their immunoregulatory effects both in vitro and in vivo.Methods
Extracellular vesicles derived from M. furfur were isolated by sequential ultracentrifugation procedure. Their structure and diameter were determined by negative stain TEM and NTA, respectively. Confocal microscopy was used to visualize the internalization of these nanoparticles into HaCaT cells and mice epidermal keratinocytes. The expressions of inflammatory cytokines were screened using PCR Array assay and validated in vitro by qPCR and ELISA assays. In vivo cytokine production was measured by the IHC method. The role of NF-κB in such process was evaluated in HaCaT cells by western blot assay.Results
Our results showed that M. furfur produced ovoid-shaped nanoparticles, which could be then internalized into HaCaT cells, as well as mice epidermal keratinocytes. IL-6 expression was significantly enhanced in response to extracellular vesicular stimulation both in vitro and in vivo, in which process the activation of NF-κB was involved.Conclusion
M. furfur has the ability to release extracellular vesicles, which can be internalized into keratinocytes and promote the production of IL-6 with the involvement of NF-κB dependent pathway. Such findings reveal some important new insights into Malassezia pathogenesis and therapy. 相似文献7.
Chihiro Imura Azumi Ueyama Yoshikazu Sasaki Masaya Shimizu Yoko Furue Nobuyuki Tai Kenichiro Tsujii Kazufumi Katayama Takayuki Okuno Michitaka Shichijo Kiyoshi Yasui Mina Yamamoto 《Journal of dermatological science》2019,93(3):176-185
Background
Retinoic acid receptor-related orphan receptor gamma t (RORγt) has critical roles in the development, maintenance and function of interleukin (IL)-17-producing cells and is a highly attractive target for the treatment of IL-17-mediated autoimmune disease, particularly psoriasis. On the other hand, RORγt is also critical for controlling apoptosis during thymopoiesis, and genetic RORγt ablation or systematic RORγt inhibition cause progressive thymic aberrations leading to T cell lymphomas.Objective
We investigated whether topical administration of our novel RORγt inhibitor, S18-000003 has therapeutic potential for psoriasis with low risk of thymic aberrations.Methods
We evaluated the effect of topical S18-000003 on psoriasis-like skin inflammation and influence on the thymus in a 12-O-tetradecanoylphorbol-13-acetate-induced K14.Stat3C mouse psoriasis model.Results
S18-000003 markedly inhibited the development of psoriatic skin inflammation via suppression of the IL-17 pathway. In the skin, S18-000003 suppressed all subsets of IL-17-producing cells that we previously identified in this psoriasis model: Th17 cells, Tc17 cells, dermal γδ T cells, TCR? cells that probably included innate lymphoid cells, and CD4?CD8? double-negative αβ T cells. Notably, neither reduction of CD4+CD8+ double-positive thymocytes nor dysregulation of cell cycling was observed in S18-000003-treated mice, even at a high dose.Conclusion
Our topically administered RORγt inhibitor is a potential therapeutic agent for psoriasis with low risk of thymic lymphoma. 相似文献8.
Ligia Aranibar Duran Jonathan Stevens González Carlos Palma Ducommun Solange Zapata Manque Javiera Pizarro Olave 《Piel》2017,32(10):604-609
Introduction
Tinea capitis (TC) is a dermatophytosis that affects the hair and scalp. The epidemiology of TC depends on the different geographical areas and is variable over time. Direct microscopic examination and fungal culture are essential to confirm the diagnostic suspicion and to identify the germ involved.Objectives
To determine the frequency of TC, to identify the etiological agents and to analyze the epidemiological aspects, in patients with suspected TC from Santiago Norte during the period 2009-2015.Materials and methods
A total of 505 patients with suspected TC were evaluated in the Dermatology Laboratory, Hospital Clinico Universidad de Chile. Direct microscopic examination was performed with KOH 30% and fungal culture of scalp lesions. Identification of the fungi was mainly morpho-physiological.Results
The diagnosis of TC was confirmed in 155 cases (30.7%). Male gender predominated (57.4%). The average age was 5 years. 85.2% of the cases occurred in the preschool and school population. The most frequent isolated agent was Microsporum canis in 89.8%, followed by Trichophyton tonsurans in 7.1%. It was confirmed that 81.8% of the cases of Trichophyton tonsurans had foreign ancestry, mainly of Haiti and Peru.Conclusions
This study evidenced the occurrence of Trichophyton tonsurans as a cause of TC, which could be explained by the increase in the immigrant population and the anthropophilic characteristics of the dermatophyte. 相似文献9.
Natsuko Noguchi Tomonori Hirose Tomoko Suzuki Masami Kagaya Kazuhiro Chida Shigeo Ohno Motomu Manabe Shin-Ichi Osada 《Journal of dermatological science》2019,93(2):101-108
Background
The epidermis possesses regenerative properties that become apparent only after wounding. Atypical protein kinase C (aPKC) isoforms aPKCζ and aPKCλ form a ternary complex with Par3 and Par6, and play crucial roles in establishing and maintaining epithelial cell polarity. The epidermal loss of aPKCλ?results in progressive depletion of hair follicle stem cells. However, it is unclear whether aPKCs have equivalent activities in epidermal regeneration.Objectives
To clarify functional differences between aPKCζ and aPKCλ in cutaneous wound healing.Methods
We compared cutaneous wound healing processes in vivo using mutant mice with genetic deletion of each aPKC isoform. We also analyzed functional differences between aPKCζ and aPKCλ in cell proliferation, directional cell migration, and formation of microtubules in vitro using primary keratinocytes established from each mutant mouse.Results
Wound healing was significantly retarded in epidermis-specific aPKCλ knockout mice. In aPKCλ-deleted keratinocytes, the correct orientation of cell protrusions toward the wound was disrupted through the destabilization of Par6β. The elongation of stabilized β-tubulin was also deteriorated in aPKCλ-deleted keratinocytes, leading to defects in cell spreading. Conversely, wound healing and directional cell migration in aPKCζ-deleted mice were comparable to those in their control littermates.Conclusions
aPKCs are not functionally equivalent; aPKCλ, but not aPKCζ, plays a primary role in cutaneous wound healing. 相似文献10.
Gizem Onal Ozlem Kutlu Ebru Ozer Devrim Gozuacik Aysen Karaduman Serap Dokmeci Emre 《Journal of dermatological science》2019,93(1):50-57
Background
Autosomal Recessive Congenital Ichthyosis (ARCI) is a group of epidermal keratinization disorders. One of the disease-associated proteins, patatin-like phospholipase domain-containing protein-1 (PNPLA1), plays a key role in the epidermal omega-O-acylceramide synthesis and localizes on the surface of lipid droplets (LDs).Objective
Previously, routine clinical test results showed abnormal LD accumulation in blood smear samples of our ARCI patients with PNPLA1 mutations. To investigate the abnormal accumulation of LDs, we analyzed primary fibroblast cells of ARCI patients with PNPLA1 mutations (p.Y245del and p.D172N). We hypothesized that PNPLA1 mutations might affect lipophagy-mediated regulation of LDs and cause intracellular lipid accumulation in ARCI patients.Methods
LD accumulation was analyzed by fluorescence staining with BODIPY®493/503 in the fibroblasts of patient cells and PNPLA1 siRNA transfected control fibroblast cells. The expression of PNPLA1 and its effects on the lipophagy-mediated degradation of LDs were analyzed by immunocytochemistry and immunoblotting.Results
Our results showed that mutant or downregulated PNPLA1 protein causes abnormal intracellular LD accumulation. We found that PNPLA1 mutations affect neither the cellular localization nor the expression levels of the protein in fibroblast cells. When we analyzed lipophagic degradation process, LC3 expression and the number of autophagosomes were significantly decreased in fibroblast cells of the patients. In addition, co-localization of LDs with autophagosomes and lysosomes were markedly less than that of the control group.Conclusion
PNPLA1 mutations caused disturbances in both autophagosome formation and fusion of autophagosomes with lysosomes. Our results indicate a possible role for PNPLA1 protein in LD regulation via lipophagy-mediated degradation. 相似文献11.
Li Zhang Yuli Kang Shujun Chen Li Wang Min Jiang Leihong Xiang 《Journal of dermatological science》2019,93(2):92-100
Background
Vitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear.Objective
To investigate the potential role of CCL20 and the involvement of Th1/17 and Tc1/17 cells in the mechanism in vitiligo.Methods
One hundred patients with vitiligo, and 20 healthy controls were included. The serum and blister fluid IL-17, IFN-γ, CCL20, and CXCL10 were studied using enzyme-linked immunosorbent assays. The numbers of Th1/17 cells and Tc1/17 cells in circulation were quantified using flow cytometry. CCR6 mRNA in peripheral blood mononuclear cells (PBMCs) was analyzed by real-time polymerase chain reaction and the protein level was confirmed by western blotting. CCR6 and CCL20 expression in lesions was analyzed by immunohistochemistry.Results
The serum CCL20 level was significantly elevated in patients with vitiligo. The level of serum CCL20 was higher in active than in the stable stage, which correlated positively with the Vitiligo European Task Force spreading score and the Vitiligo Area Scoring Index score. Patients with active vitiligo had elevated numbers of circulating Th1/17 cells and Tc1/17 cells, and upregulated expression of CCR6 in PBMCs and lesions. After effective treatment, the level of CCL20 in sera and blister fluid was significantly decreased, as were the numbers of circulating Th1/17 cells and Tc1/17 cells.Conclusion
CCL20 might be a vital biomarker of active vitiligo, and circulating Th1/17 and Tc1/17 cells are involved in the pathogenesis of vitiligo. 相似文献12.
Arturo César Argote Ruiz Óscar Mora Hernández Lilian Torres-Tobar Marcela Gómez Garzón Carlos Reverend Catherine Alba Ayala Joanna Cajamarca Rueda Alejandra Toquica Díaz 《Piel》2019,34(4):204-211
Background
Acne is one of the most common reasons for consultation in dermatology. It affects the most adolescents and brings psychosocial consequences that alter their quality of life. Among the pathophysiological aspects is the colonization by Cutibacterium acnes (C. acnes) of which currently have been described 6 phylotypes (IA1, IA2, IB, IC, II, and III) related to their inflammatory potential.Objective
To identify the phylotypes of C. acnes in the lesions of patients with acne who consulted the Dermatology Department at Hospital San José, Bogotá, Colombia.Methods and materials
A 90 samples of acne patients pustules were collected. The bacterium was identified in culture by anaerobic conditions. The isolates where subjected to antibiotic sensitivity tests and subsequently processed and analysed using Microflex? LT MALDI-TOF.Result
57.78% of the isolates corresponded to the genera Propionibacterium and Cutibacterium; of these, 65.38% were C. acnes, typified by mass spectrometry. The phylotypes found were of type IA1, IA2, IB, and II in 5.88%, 85.29%, 2.94%, and 5.88%, respectively.Conclusions
The phylotype IA2 was the most frequently identified, a result that differs from data reported in non-Latin American studies in which the IA1 is the predominant, this relevant finding opens new questions about the behavior of C. acne in different populations. It also reports the global antibiotic resistance to the phylotypes to the four antibiotics most commonly used in clinical practice, finding greater resistance to erythromycin, followed by clindamycin, and in a lesser proportion to doxycycline and tetracycline. 相似文献13.
Saki Maeda-Otsuka Ikko Kajihara Yukino Tasaki Saori Yamada-Kanazawa Ryoko Sakamoto Soichiro Sawamura Mamiko Masuzawa Mikio Masuzawa Yasuyuki Amoh Daichi Hoshina Riichiro Abe Yoshihiro Komohara Hironobu Ihn 《Journal of dermatological science》2019,93(2):123-132
Background
Angiosarcoma is a rare malignant tumor with a poor prognosis. It is known that hypoxic condition activates tumor progression in several cancers. Additionally, hypoxic tumor microenvironment accelerates immune escape. However, the presence and significance of hypoxia in angiosarcoma has not been adequately investigated.Objective
To study the role of hypoxia in the progression of angiosarcoma.Methods
The protein level of hypoxia inducible factor-1α (HIF-1α) in angiosarcoma was examined using immunohistochemistry and immunoblotting. To study the effect of hypoxia on tumor progression, cell proliferation, migration, invasion, and tube formation assays were performed in angiosarcoma cells. The influence of tumor cell supernatant in hypoxia from angiosarcoma cells on immune escape and angiogenesis was analysed to investigate the modulatory effect of hypoxia on tumor microenvironment of angiosarcoma. The molecular mechanism related to these results was investigated using immunoblotting and real time RT-PCR.Results
HIF-1α protein was over-expressed in angiosarcoma tissues and cell lines under hypoxic conditions, and there was heterogeneity of oxygen supply in angiosarcoma. Hypoxia enhanced the proliferation, migration, and invasion abilities and inhibited tube formation in angiosarcoma cells. Tumor cell supernatant in hypoxia from angiosarcoma cells activated the monocyte invasion ability, facilitated its differentiation into M2-like macrophages, and suppressed cell-adhesion. These in vitro results were compatible to the pathological findings of angiosarcoma patients.Conclusion
Hypoxia plays a major role in progression of angiosarcoma cells by enhancing cell proliferation, migration, and invasion and by modulating the tumor microenvironment. 相似文献14.
M. Ribera S. Ros B. Madrid R. Ruiz-Villaverde F. Rebollo S. Gómez E. Loza G. Carretero 《Actas dermo-sifiliográficas》2019,110(2):102-114
Objective
To establish recommendations to determine, identify, and manage the psychological and emotional needs of patients with chronic inflammatory skin diseases in clinical practice.Methods
A guided discussion was held at meeting of a nominal group of expert dermatologists and psychologists on the psychological and emotional needs of patients with chronic inflammatory skin diseases, how to manage these cases, and which referral criteria to employ. Based on the results of the discussion, and with the aid of a patient focus group and a review of the literature, a master document was drawn up with recommendations for discussion. A Delphi survey was circulated among a larger group of dermatologists and psychologists to assess the level of agreement with the recommendations.Results
Ten recommendations were established and can be summarized as follows: explore the psychological sphere of the patients with open questions at the time of diagnosis and during the course of the disease; provide patients with clear explanations that address their concerns and inform them of the existence of patient associations; investigate symptoms of anxiety and depression and, if confirmed by means of a Hospital Anxiety and Depression score (HADS) of 11 or greater, consider referral to a mental-health specialist; and, during visits, create a climate of trust, empathize with patients, agree goals and treatment options with them, and motivate them to adhere to those treatments.Conclusions
These recommendations may help health care professionals address psychological and emotional aspects of their patients in daily clinical practice. 相似文献15.
16.
Yosuke Kubo Satoshi Fukushima Yukiko Inamori Mina Tsuruta Sho Egashira Saori Yamada-Kanazawa Satoshi Nakahara Aki Tokuzumi Azusa Miyashita Jun Aoi Ikko Kajihara Yusuke Tomita Kazumasa Wakamatsu Masatoshi Jinnin Hironobu Ihn 《Journal of dermatological science》2019,93(1):33-40
Background
Anti-programmed cell death protein (PD)-1 antibody treatment is associated with a notable improvement in only 30%–40% of patients. Thus, a predictive and easily measured marker of the clinical benefit of anti-PD-1 antibody treatment is necessary; therefore, in this study, we focused on the serum concentration of hepatocyte growth factor (HGF).Objectives
To evaluate whether the serum concentration of HGF can be used as a biomarker for the clinical response to anti-PD-1 antibody therapy.Methods
This study included 29 metastatic melanoma patients receiving nivolumab or pembrolizumab. Nine patients responded to anti-PD-1 antibody treatment, whereas the other 20 patients did not. The serum concentrations of HGF were analyzed by using ELISA. In 28 patients, immunohistochemical analysis of the HGF protein in patients’ cancer tissues was also performed. Peripheral blood mononuclear cells (PBMCs) from healthy donors were cultured with an anti-CD3 antibody in the presence or absence of HGF and c-MET inhibitor. The expression of perforin in CD8+ T cells were evaluated by using flow cytometry.Results
Among the 29 recruited patients, the non-responders displayed higher serum concentrations of HGF than the responders (P?=? 0.00124). Patients with low serum concentrations of HGF showed longer overall survival (N?=?28, P?=? 0.039; HR 0.3125, 95% CI 0.1036–0.9427) and progression-free survival (N?=?24, P?=? 0.0068; HR 0.2087, 95% CI 0.06525–0.6676) than those with high concentrations of HGF. We observed a significant correlation between the serum concentration of HGF and immunohistochemical-positive staining (P?=? 0.000663). In a flow cytometry analysis of PBMCs from healthy donors, HGF was found to downregulate perforin secretion. Furthermore, the addition of capmatinib, a specific inhibitor of c-MET, increased the expression of perforin in CD8+ T cells.Conclusions
HGF concentration represents a valid biomarker that can be further developed for the evaluation of anti-PD-1 therapy. Our results suggested that c-MET inhibition promotes perforin expression in CD8+ T cells. Therefore, c-MET inhibitors can activate the immune system and may play an important role in combined immunotherapy. 相似文献17.
Kimiko Nakajima Sayo Kataoka Kenji Sato Mikiro Takaishi Mayuko Yamamoto Hideki Nakajima Shigetoshi Sano 《Journal of dermatological science》2019,93(2):82-91
Background
Psoriasis is an inflammatory disease associated with aberrant crosstalk between the epidermis and immune system. However, the role of Langerhans cells (LCs) in psoriasis remains controversial.Objectives
To elucidate whether LCs are functionally involved in the development of psoriasis using a mouse model.Methods
Two lines of transgenic mice were used and crossed. They included K5.Stat3C, the psoriasis-model mouse and langerin DTR knock-in (KI) mouse. We performed immunofluorescence staining for LCs in psoriatic lesion of human and model mice. Flow cytometric analyses were performed to compare between dendritic cells (DCs) and LCs in the epidermis and skin-draining lymph nodes (sDLNs). To assess cytokine/chemokine expression in the skin lesion or primary cultured keratinocytes, we performed RT-PCR, microarray analysis or intracellular staining on the flow cytometer.Results
LCs were activated in psoriatic lesion of patients with psoriasis and K5.Stat3C mice. Compared with non-transgenic mice, K5.Stat3C mice constitutively showed an increased number of LCs in the sDLNs before psoriasis-like lesion developed. Stat3C transgenic keratinocytes expressed an elevated level of IL-1α. Psoriasis-like lesion in K5.Stat3C mice were attenuated in the absence of LCs, indicating that LCs were essential to the development of psoriasis-like lesion. Furthermore, we also recognized that epidermal LCs in psoriatic lesion of not only K5.Stat3C mice but also psoriasis patients produced IL-23.Conclusions
Our study suggests that Stat3 activation in keratinocytes may impact on LC activation in situ via IL-1α stimulation, at least in part, and that their presence may be essential for the pathogenesis of psoriasis through producing IL-23. 相似文献18.
Lula María Nieto Benito Ángel Manuel Rosell Díaz Ana Mateos Mayo Carmen Rodríguez Sáinz Ricardo María Suárez Fernández Ofelia Baniandrés Rodríguez 《Piel》2019,34(5):266-271
Introduction
Palmoplantar pustulosis (PPP) is characterised by the presence of sterile association with other diseases differ among published studies. IL36RN gene mutation has recently been identified in patients with mainly generalised pustular forms, but also in some patients with PPP. The objective of this study is to describe clinical and epidemiological characteristics, the incidence of inflammatory diseases in PPP, and to study the frequency of IL36RN gene mutations.Methods
An observational, retrospective, longitudinal study is presented, which includes all patients attended in our centre between 2009 and 2017 with a PPP diagnosis if only they were controlled by photography.Results
41 patients were included (90% women; average age of 55, 8). 94% were smokers or ex-smokers, 24% had a history of plaque psoriasis, 39% ungueal psoriasis and 27% a positive familiar background. On analysing IMIDs (immune mediated inflammatory disorders) incidence in PPP patients, 7% had inflammatory bowel disease, 10% psoriatic arthritis, and 22% other types of arthritis. No IL36RN gene mutations were found in any of the 11 patients in whom a genetic study was performed.Conclusions
Patients with PPP are mostly women who smoke, in the fifth decade of life, with an incidence of IMIDs higher than expected, as well as with a high prevalence of personal and family history of psoriasis. 相似文献19.
20.