MICROCHIMICA ACTA
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2025
·Vol. 192
·期 5
·1-9
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IF 5.3
Li Rui,Que Wenzhong,Han Haiyan,Shi Honghui,Wang Rongfeng,Qiu Bin
IL-17 (interleukin-17) is a common proinflammatory cytokine and can be adopted as an important biomarker for several diseases; it is thus very necessary to design an effective method for monitoring IL-17. Herein, by preparing silver nanoparticles/graphdiyne (Ag/GDY) with simple electroless deposition as the sensing platform and methylene blue/UiO-66-NH 2 MOFs (MB/MOFs) as the signaling-amplifier, a highly efficient sandwich-like electrochemical immunosensing (SLEI) platform was designed for IL-17 detection. The superior electrical property, easy preparation, large surface area, and high stability of Ag/GDY make it a desirable substrate to immobilize primary antibody of IL-17. Meanwhile, the unique structure of UiO-66-NH 2 is beneficial to immobilize MB probe and secondary antibody. By optimizing experimental conditions, the MB current obtained at the as-designed SLEI platform increases along with IL-17 increase, and the related linearity is 1.0 pg mL −1 –1.0 ng mL −1 coupled with a low detection limit of 0.3 pg mL −1 . It is expected that the SLEI platform based on Ag/GDY and MB/MOFs shows some potential application for IL-17 detection. Graphical abstract
研究领域:
生物医学工程
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免疫学
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材料科学
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PubMed
高影响因子
Nature Communications
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2025
·Vol. 16
·期 1
·1-19
·
IF 15.7
Shen Xuecheng,Qiao Wenxuan,Yan Wei,Xie Hao,Zhang Chenyang,Sun Yang,Luo Qiong,Xu Qiang
IL-17 signaling contributes to the pathogenesis of psoriasis; however, IL-17 involvement in keratinocyte hyperactivation of epidermis remains unclear. Here, we describe an IL-17A-induced, skin-specific, positive feedback loop, which operates independently of canonical chemokine production, thus untangling skin inflammation and epithelial hyperproliferation in psoriasis. We show that IL-17A-induced, keratinocyte-specific KLK8 interacts with IL-17R to promote histone H4 lysine lactylation (H4K12la) catalyzed by the acetyltransferase HAT1. H4K12la further promotes IL-17A-mediated keratinocyte proliferation and the expression of KLK8 and IL-17R, creating a feedback loop that drives psoriasis progression. Importantly, excessive lactate in the microenvironment exacerbates H4K12la and psoriasis severity, thereby impairing the efficacy of anti-IL-17A antibody. Silencing KLK8, HAT1, or inhibiting lactate accumulation attenuates psoriasis in mice. Moreover, combining lactylation inhibition with anti-IL-17A therapy exhibits synergistic effects against antibody-resistant psoriasis. Thus, our findings unveil a lactylation-driven, keratinocyte-specific IL-17A signaling and offer a promising approach for psoriasis treatment, particularly in patients with comorbid metabolic syndrome.
研究领域:
皮肤生物学
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表观遗传学
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免疫学
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分子生物学
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炎症性疾病
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转化医学
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PubMed
高影响因子
International Journal of Medical Sciences
·
2025
·Vol. 22
·期 4
·856-872
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IF 3.2
Li Bowei,Yang Jingyuan,Wang Zhixing,He Mingzhu,Chen Xujing,Chen Yixuan,Shen Baoying,Chen Junru,Yang Chunqi,Li Tian,Lai Chengcai,Gao Yue,Cai Hong
Introduction: Solar dermatitis, a condition triggered by excessive exposure to ultraviolet B (UVB) radiation, results in inflammatory skin damage marked by erythema, edema, and epidermal injury. Portulaca oleracea (PO) and Patrinia scabiosaefolia (PS) have been traditionally used in dermatological treatments, though their mechanistic pathways in UVB-induced skin injury are not fully understood.Methods: In this study, a mouse model of UVB-induced solar dermatitis was employed to evaluate the therapeutic potential of combined PO and PS (POPS) extracts. After UVB irradiation, POPS extracts were administered, and their bioactive compounds were identified through ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Network pharmacology, molecular docking, and pathway analysis were performed to identify key targets, focusing on the IL-17/CCL2 pathway and oxidative stress reduction.Results: Treatment with POPS extracts significantly diminished UVB-induced inflammation, erythema, and epidermal thickening in a dose-dependent manner. Network pharmacology and docking studies identified curvularin and olmesartan medoxomil as bioactive components with high affinity for IL-17 and IL-17RA targets, modulating the IL-17/CCL2 axis. In vivo experiments demonstrated that POPS extracts suppressed the expression of IL-17 and CCL2, reduced macrophage infiltration, and alleviated oxidative stress, effectively mitigating the symptoms of solar dermatitis.Conclusion: This study provides insight into the anti-inflammatory and protective properties of POPS extracts in solar dermatitis, highlighting their potential as a treatment through IL-17/CCL2 pathway modulation and oxidative stress reduction.
研究领域:
药理学
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皮肤病学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Abudureyimu Alimujiang,Hongzhi Wang,Liangmian Chen,Yutong Kang,Jingcheng Zhao,Wenjing Wei,Shixia Huo,Dengqiu Xu,Zhijian Li
Ethnopharmacological relevance Psoriasis is a chronic immune-mediated skin disease characterized by the infiltration of multiple inflammatory cells and abnormal differentiation of keratinocytes in the skin. The treatment of psoriasis is primarily based on immunosuppressive drugs; however, their long-term use can lead to various adverse effects. Euphorbia humifusa Willd. (EuH) is used in traditional Chinese medicine for its anti-inflammatory properties and effects on skin diseases such as psoriasis. Aim of the study This study aimed to evaluate the anti-psoriasis effects of EuH extract, and explore its underlying mechanisms. Methods and materials The main components of EuH extract were analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) technology. Then, we administered EuH extract to imiquimod-induced psoriasis mice for 6 consecutive days, and evaluated the effects according to the psoriasis area and severity index (PASI), spleen index, histological analysis, immunohistochemical and immunofluorescence staining, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and flow cytometry analysis. The potential mechanism was revealed using RNA sequencing (RNA-seq) and validated by target prediction, ELISA, qRT-PCR and western blot (WB) analysis. Results The UPLC-QTOF-MS/MS analysis showed that phenolics were the essential components in the water extracts of EuH, including flavonoids, phenolic acids, and gallotannins. Treatment with EuH alleviated psoriatic symptoms including skin condition, high PASI scores (erythema, scaling, and thickness), and spleen index values in imiquimod-induced mice. EuH treatment also inhibited keratinocyte hyperproliferation, reduced epidermal thickness, reduced inflammatory cell infiltration into skin lesions, decreased the mRNA levels of inflammatory factors, and restored T and Treg cellular balance in the spleen. RNA-seq, ELISA, qRT-PCR and WB analyses indicated that EuH extract reduced the inflammatory response and keratinocyte hyperproliferation by inhibiting the IL-17 signaling pathway. Conclusions Our findings suggest that EuH extract suppresses keratinocyte hyperproliferation and inflammation in psoriasis by inhibiting the IL-17 signaling pathway, supporting EuH as a potential treatment for psoriasis.
研究领域:
药理学
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皮肤病学
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免疫学
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DOI
PubMed
高影响因子
Reproductive Sciences
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2023
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IF 2.9
Shao Mingkun,Hou Mengyao,Li Sainan,Qi Wenjin
Vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are the most common lower genital tract infections in reproductive women. In recent years, the research on its pathogenesis mainly focuses on vaginal local immunity and IL-17 as key factors in adaptive immunity, attracting much attention. However, the role of IL-17 in local immunity in VVC and RVVC is poorly understood. At the same time, neutrophils are considered the most effective way to control and eliminate candidal infection and have a controversial role in VVC and RVVC. In this study, we built a mouse RVVC model. After analyzing the vaginal lavage solution of RVVC mice with an inflammatory factor antibody chip and ELISA, we found that IL-17 may play a protective role in RVVC. The experiment of constructing RVVC mice with different concentrations of IL-17 using halofuginone and comparing the vaginal fungi load and vaginal epithelial damage verified that IL-17 had a protective effect in RVVC. In addition, in vitro and in vivo studies found that IL-17 can promote neutrophil apoptosis and recruit neutrophils in the vagina. The neutrophils in the vagina can secrete IL-17 in an autocrine manner. These two may be why IL-17 plays a protective role in RVVC. In summary, the study suggests that IL-17-mediated regulation of neutrophil function is involved in host immune response to RVVC, which helps us to further understand the potential mechanism of IL-17 in RVVC.
研究领域:
免疫学
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微生物学
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传染病学
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分子生物学
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PubMed
高影响因子
ANDROLOGIA
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2022
·Vol. 54
·期 8
·e14455
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IF 2.532
Cheng Zhang,Jia Chen,Hui Wang,Jing Chen,Mei-Juan Zheng,Xian-Guo Chen,Li Zhang,Chao-Zhao Liang,Chang-Sheng Zhan
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a poorly understood disease. Accumulating evidence suggests that autoimmune dysfunction is involved in the development of CP/CPPS. Interleukin-17 (IL-17) is associated with the occurrence and development of several chronic autoimmune inflammatory diseases. However, the molecular mechanisms underlying the role of IL-17 in CP/CPPS are not clear. We confirmed that IL-17 was increased in the prostate tissues of experimental autoimmune prostatitis (EAP) mice. Corresponding to the increase of IL-17, neutrophil infiltration and the levels of CXCL1 and CXCL2 (CXC chemokine ligands 1 and 2) were also increased in the prostate of EAP. Treatment of EAP mice with an IL-17-neutralizing monoclonal antibody (mAb) decreased the number of infiltrated neutrophils and CXCL1 and CXCL2 levels. Depletion of neutrophils using anti-Ly6G antibodies ameliorated the inflammatory changes and hyperalgesia caused by EAP. Fucoidan, a could potent inhibitor of neutrophil migration, also ameliorate the manifestations of EAP. Our findings suggested that IL-17 promoted the production of CXCL1 and CXCL2, which triggered neutrophil chemotaxis to prostate tissues. Fucoidan might be a potential drug for the treatment of EAP via the effective inhibition of neutrophil infiltration.
研究领域:
免疫学
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泌尿学
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炎症
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自身免疫性疾病
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
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2022
·Vol. 36
·期 10
·3969-3987
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IF 6.388
Yi Chen,Shasha Song,Yongfang Wang,Jia Zhu,Xinyu Li
Psoriasis (PSO), an immune-mediated chronic inflammatory skin disease, has seriously affected the quality of patients' life. It is urgent to find effective medicines with lower costs and less side effects. Baicalin (HQG) is the main bioactive substance from Scutellaria baicalensis with effects of anti-inflammation and immunoregulation. Herein, we explored the effect of oral HQG treating PSO and its potential mechanism. Firstly, network pharmacology was used to predict that HQG may act on Estrogen, TNF-alpha (tumor necrosis factor, TNF), interleukin-17 (IL-17) signaling pathways and Th17 cell differentiation, especially the key targets including TNF, Proto-oncogene tyrosine-protein kinase Src, Peroxisome proliferator-activated receptor gamma and Matrix metalloproteinase-9. Imiquimod (IMQ)-induced mice were then used to study the effects of HQG treating PSO. HQG could significantly ameliorate the skin lesions, decrease the level of inflammatory factors and inhibit Th1/Th17 cell differentiation in IMQ-induced mice. Finally, transcriptome analysis of skin lesions integrated with the prediction of network pharmacology further demonstrated that the potential mechanism may be associated with suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPARγ. In conclusion, this study suggested that HQG may be a promising agent for further studies in the search for therapeutic strategies to treat PSO in the future.
研究领域:
药理学
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免疫学
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皮肤科
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Huan Song,Guo-Qiang Liang,Man-Shu Yu,Yun Shan,Jun Shi,Chun-Bo Jiang,Dao-Lei Ni,Mei-Xiao Sheng
Ethnopharmacological relevance Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world, it is one of the most common causes of kidney disease and can lead to end-stage kidney disease, however, its pathogenesis is still complicated. The Shen-yan-yi-hao oral solution (SOLI) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated. Aim of the study This study investigates SOLI's effects on IgAN in rats, particularly on the intestinal mucosal barrier, and identifies potential therapeutic targets through network pharmacology and molecular docking, validated experimentally. Materials and methods Target genes for SOLI in IgAN were identified and analysed through molecular docking and KEGG pathway enrichment. An IgAN rat model examined SOLI's effect on renal biomarkers and cytokines involved in specific pathways, ileum mucosal lesions, and the intestinal immune system. The IL-17 pathway's role was studied in IEC-6 cells with SOLI in vitro. Result Rats developed increased proteinuria and kidney damage marked by IgA deposition and inflammation. SOLI treatment significantly ameliorated these symptoms, reduced galactose-deficient Ig A1 (Gd-IgA1), and decreased cytokines like IL-17, TNF-α, IL-6 and IL-1β etc. SOLI also normalized intestinal tight junction protein expression, ameliorated intestinal damage, and regulated intestinal immune response (focused on IL-17/NF-κB signal pathway). SOLI moderated the abnormally activated IL-17 pathway, which damages intestinal epithelial cells, suggesting IgAN treatment potential. Conclusion SOLI reduces proteinuria and enhances intestinal mucosal function in IgAN rats, kidney protection in the IgAN rat model may initiate from modulating the intestinal IL-17/NF-κB pathway and subsequent Gd-IgA1 accumulation.
研究领域:
药理学
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免疫学
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肾病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
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2018
·
IF 3.061
Qin Zhu,Peifen Zheng,Xinyu Chen,Feng Zhou,Qiaona He,Yuefeng Yang
Ulcerative colitis (UC) is a chronic and nonspecific intestinal inflammatory disease, which may increase the risk of colon cancer. Andrographolide is a main active component of Andrographis paniculata . The anti-inflammatory ability of andrographolide suggested its potential therapeutic effect against UC. In the present study, elevated serum concentrations of proinflammatory factors, including (TNF)-α, interleukin (IL)-1β, IL-6 and IL-23, as well as increased percentages of Th17 cells (IL-17+CD4+ cells) in CD4+ cells were detected in UC patients compared to that in healthy donors. These data suggested that Th17 immune responses may involve in the pathogenesis of UC. Experimental colitis mouse model was then established. The results of hematoxylin and eosin staining demonstrated the therapeutic effect of andrographolide on colitis. Enzyme-linked immunosorbent assay (ELISA), flow cytometry and western blotting analyses showed that andrographolide could decreased the levels of proinflammatory factors TNF-α, IL-1β, IL-6 and IL-17A in the serum and in the colon tissues, reduced the percentages of Th17 cells in CD4+ cells, and suppressed the levels of IL-23, IL-17A, ROR-γt (key transcription factor of Th17 cells) and p-STAT3 in the colon tissues. Further, peripheral blood mononuclear cells (PBMCs) were isolated from UC patients and treated with various concentrations of andrographolide (0, 10, 20 and 30 μg/ml). Andrographolide also showed inhibitory effects on the levels of proinflammatory factors, the percentages of Th17 cells and the expression of relative proteins. Similar results were obtained in lipopolysaccharide-treated normal PBMCs. These data suggested that andrographolide may inhibit Th17 immune response via STAT3 signaling. In conclusion, we demonstrated that andrographolide inhibited the activity of IL-23/IL-17 axis and down-stream pro-inflammatory factors so as to suppress inflammation response, resulting in the relieving of UC.
研究领域:
免疫学
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药理学
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炎症性肠病
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2024
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IF 6.7
Yunyi Xu,Qionghua Ding,Yuhuan Xie,Qingqing Zhang,Yangyu Zhou,Hairui Sun,Rui Qian,Liqun Wang,Xuxi Chen,Ying Gao,Yuqin Yao,Yue Xiao
Background Silicosis, an interstitial lung disease caused by inhalation of silica particles, poses a significant health concern globally. Green tea polyphenol (TP) stands out as a promising therapeutic candidate, yet its specific protective effects and in-depth mechanisms against silicosis have not been thoroughly investigated. Purpose This study aimed to systematically assess the protective potential of TP against silicosis and to elucidate the underlying mechanisms of its action. Methods A combination of physiological, transcriptomic, molecular, and computational techniques was employed. HPLC was used to identify the components of TP, and its antioxidant properties were tested with DPPH and ABTS assays. The effects of TP on lung injury were assessed in silicosis mice using histopathology, qRT-PCR, and western blot. Transcriptomic analysis was applied to explore the differentially expressed genes and pathways in response to TP intervention. In vitro studies with mouse alveolar macrophages (MH-S) examined TP's effects on cell viability, proliferation, apoptosis, and inflammation responses. Integrated qRT-PCR, western blot, immunohistochemistry, and molecular docking were performed to confirm the molecular mechanism underlying the protective effects of TP against silicosis. Results TP effectively attenuated pulmonary inflammation and fibrosis in silicosis mice, as evidenced by significant reductions in inflammation and fibrotic markers. Moreover, TP's therapeutic benefits were linked to its cytoprotective effects on alveolar macrophages, notably its ability to protect MH-S cells from silica particle-induced apoptosis, inhibition of proliferation, and inflammatory response, underscoring its targeted protective effects at the cellular level. Mechanistically, TP exerted its anti-silicosis activity by targeting key pathways implicated in inflammatory responses, notably through the inhibition of the IL-17/NF-κB p65 signaling cascade. Molecular docking simulations corroborated these findings, demonstrating favorable binding affinities between TP's bioactive components (EGC, ECG, and EGCG) and crucial proteins (IL-17A, IL-17F, p65, TNF-α, IL-6, and IL-1β) involved in the IL-17/NF-κB p65 signaling pathway. This pathway inhibition led to a significant decrease in the production of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, thus mitigated silicosis. Conclusion TP demonstrates efficacy in alleviating silica particle-induced lung injury by suppressing inflammation through the IL-17/NF-κB p65 signaling pathway, underscoring its potential as a valuable natural compound for silicosis management.
研究领域:
肺科学
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药理学
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免疫学
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分子生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
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2026
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IF 11
Hongyun Xuan,Zihao Liu,Keyu Lu,Yao Chen,Haonan Gu,Biyun Li,Jingjun Sun,Yan Jin,Yumin Yang,Huihua Yuan
Diabetic wound repair remains a formidable clinical challenge due to impaired healing and heightened infection risks associated with conventional sutures. To address these limitations, this study introduces a novel injectable, self-healing, and antibacterial polysaccharide hydrogel (PGHAA), synthesized from borated peach gum and oxime-modified hyaluronic acid. By leveraging dynamic boronic ester bonds and metal coordination, PGHAA demonstrates enhanced tissue adhesion, self-healing capabilities, and antibacterial activity with immunomodulatory capacity to reprogram chronic wounds into a regenerative state. The incorporation of arginine as a cross-linking agent further improves both biocompatibility and functional performance. In vitro and in vivo evaluations indicate that PGHAA facilitates rapid hemostasis, robust tissue adhesion, and macrophage polarization toward a pro-regenerative phenotype, resulting in accelerated diabetic wound healing. Using an in vivo study with chronic diabetic skin we demonstrated that PGHAA induced wound healing via modulation of IL-17/NF-κB signaling—a pathway repurposed from its classical inflammatory role to drive tissue regeneration. This work redefines diabetic wound therapy by introducing a first-in-class hydrogel that leverages immune modulation for tissue repair, offering a transformative solution for regenerative medicine.
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PubMed
高影响因子
Journal of Neuroinflammation
·
2025
·Vol. 22
·期 1
·268
·
IF 10.1
Li Shumei,Wang Lei,Luo Qiqi,Fan Maiying,Xu Yixiao,Liu Xiehong,Zhang Yiyuan,Zou Lianhong
IntroductionCardiac arrest (CA) is a life-threatening emergency with a global one-year survival rate of 2%-10%. Brain injury significantly impacts CA outcomes, and neuroinflammation is a key mediator of cerebral damage. Interleukin-17 (IL-17) has been implicated in multiple inflammatory disorders, yet its contribution to CA-induced cerebral damage remains undefined.ObjectiveTo elucidate the role of the IL-17 axis in CA-triggered neuroinflammation and to determine whether IL-17 blockade can attenuate hippocampal injury and improve neurologic recovery.Methods Asphyxial CA was induced in adult Sprague-Dawley rats followed by cardiopulmonary resuscitation. Blood–brain barrier (BBB) integrity, Th17 infiltration, astrocyte polarization, and downstream signaling were assessed by flow cytometry, RNA-seq, qRT-PCR, ELISA, immunofluorescence, and western blotting. IL-17 A or IL-17RA was neutralized in vivo with specific antibodies, and human SVGP12 astrocytes were employed for mechanistic validation.Results CA promotes Th17 cell differentiation and enhances blood-brain barrier (BBB) permeability, facilitating the infiltration of Th17 cells and their secreted IL-17 A/F into the hippocampus. IL-17 A/F specifically binds to IL-17RA/RC on astrocytes, activating NF-κB, and MAPK pathways, which drive A1 polarization of astrocytes and exacerbate neuroinflammation. IL-17 A neutralization reverses A1 polarization of astrocytes, reduces neuronal apoptosis, improves 24-hour neurologic deficit scores, and enhances survival in CA rats. In vitro, IL-17 A induced A1 polarization and inflammatory cytokine release in astrocytes, effects abolished by IL-17RA blockade.Conclusion Our study elucidates the mechanisms underlying CA-induced neuroinflammation and identifies the IL-17 A pathway as a potential therapeutic target for mitigating neurological injury following cardiac arrest.
研究领域:
神经科学
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免疫学
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重症医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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