Journal of Materials Chemistry B
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2020
·Vol. 9
·期 7
·1867-1876
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IF 5.344
Man Luo,Fujian Zhao,Lu Liu,Zhen Yang,Ting Tian,Xiaoyu Chen,Xiaodong Cao,Dafu Chen,Xiaofeng Chen
The macrophage-dominated bone immune response plays an important role in osteogenesis of bone defects. Generally, M2 macrophages are beneficial to promote osteogenesis. However, recent studies have confirmed that M1 also plays an important role in early angiogenesis, osteointegration. Therefore, achieving sequential polarization of macrophages from M1 to M2 may be more beneficial for osteogenesis. In this study, a new type of bone immunomodulatory IFN-γ/Sr-dropped bioactive glass composite scaffold (IFN-γ/SrBG) was successfully prepared which integrates multiple biological functions at different stages of the bone healing process. The scaffold can polarize macrophages into pro-inflammatory M1 type at the early stage of implantation by releasing IFN-γ within the first day, and then polarize macrophages into anti-inflammatory M2 type at a later stage by releasing Sr2+ from SrBG, which promoted mature bone formation in bone defects to a greater extent. Therefore, IFN-γ/SrBG scaffolds are expected to become excellent bone tissue engineering materials by sequential regulation of macrophage polarization.
研究领域:
生物材料
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组织工程
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免疫学
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骨科
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PubMed
高影响因子
FOOD AND AGRICULTURAL IMMUNOLOGY
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2023
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IF 3
Linyang Song,Xiaoyi He,Mengxia Wang,Lixia Li,Jing Liu,Guoying Li,Junhua Yang
People often simultaneously expose to acceptable/tolerable daily intake of food additives and pesticides in daily life. Exposure in adult rodents to acceptable/tolerable daily intake of food additives and pesticides chemical mixtures (AFACM) is reported to cause health damage. Our recently study reported that AFACM exposure of pregnant mice resulted in neuroinflammation and abnormal emotional behaviours in offspring. Here, we found that neutralising IFN-γ with neutralising antibodies completely blocked the influences induced by maternal AFACM exposure, including the increased IFN-γ level in serum, increased IFN-γ, interleukin-6 and tumour necrosis factor-α levels in prefrontal cortex(PFC) in offspring on postnatal day(PND)7, the abnormal emotional behaviours in offspring on PND56, and the decreased of ATPase phospholipid flippase 8A2(ATP8A2) in the PFC of offspring on PND7. In sum, maternal AFACM exposure induced the PFC neuroinflammation, abnormal emotional behaviours and decreased PFC ATP8A2 expression through increasing systemic IFN-γ in offspring.
研究领域:
神经科学
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免疫学
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毒理学
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行为科学
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2021
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IF 9.776
Qian Li,Yaxin Zhou,Weidong He,Xiaomeng Ren,Mengzhu Zhang,Yue Jiang,Zhaocai Zhou,Yuxia Luan
Interferon-γ (IFN-γ) plays contradictory roles in tumor immunology: (I) to activate positive host's immunity for eliminating tumor; (II) to induce negative adaptive immune resistance via up-regulating programmed death ligand-1 (PD-L1) expression for tumors to evade immune surveillance. The negative feedback loop between the IFN-γ recovery and the IFN-γ-induced PD-L1 up-regulation puts postoperative adjuvant chemotherapy into a dilemma. It is of great significance but challenging to manipulate the double-edge effects of IFN-γ against postoperative tumor progression. Herein, a platelet-engineered nanoplatform ( [email protected] NPs) capable of harmonizing janus-faced nature of IFN-γ was designed via uniquely co-assembling doxorubicin (Dox) and cyclin-dependent kinase 5 inhibitor roscovitine (Rosco) with platelet membrane fragment (PMF) as the particulate stabilizer . With [email protected] NPs navigated by PMF to residual tumor, the Dox-activated immune response recovered IFN-γ secretion for positive host's immunity, while the IFN-γ-induced negative adaptive immune resistance was potently overcome by Rosco via disabling PD-L1 expression without dependence of IFN-γ stimulation. The negative feedback loop between IFN-γ recovery and PD-L1 up-regulation was thus potently disrupted in postoperative adjuvant chemotherapy. Our [email protected] NPs not only harmonized janus-faced nature of IFN-γ to effectively regulate postoperative tumor progression, but also illustrated an innovative strategy for high-drug-loading biomimic nanoplatform.
研究领域:
肿瘤学
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免疫学
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纳米技术
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药学
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DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2024
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IF 4.1
Ting Yu,Meng Xie,Kai Luo,Xiao Zhang,Weihua Gao,Qiaoqing Xu,Shuhuan Zhang
IFN-γ plays a crucial role in both innate and adaptive immune responses and is a typical Th1 cytokine that promotes Th1 response and activates macrophages. When macrophages were incubated with IFN-γ, their phagocytosis ratio against Mycobacterium marinum increased significantly, as observed under fluorescence microscopy. The macrophages engulfed a large number of M. marinum . The proliferative ability of macrophages treated with IFN-γ was significantly weaker on the 4th and 7th day after phagocytosis and subsequent re-infection with marine chlamydia (P < 0.001). This suggests that IFN-γ enhances the phagocytosis and killing ability of macrophages against M. marinum . IFN-γ protein also significantly increased the production of reactive oxygen species (H 2 O 2 ) and nitric oxide (NO) by macrophages. Additionally, the expression levels of toll-like receptor 2 ( tlr2 ) and caspase 8 ( casp8 ) were significantly higher in macrophages after IFN-γ incubation compared to direct infection after 12 h of M. marinum stimulation. Apoptosis was also observed to a higher degree in IFN-γ incubated macrophage. Moreover, mRNA expression of major histocompatibility complex (MHC) molecules produced by macrophages after IFN-γ incubation was significantly higher than direct infection. This indicates that IFN-γ enhances antigen presentation by upregulating MHC expression. It also upregulates tlr2 and casp8 expression through the TLR2 signaling pathway to induce apoptosis in macrophages. The pro-inflammatory cytokine showed an initial increase followed by a decline, suggesting that IFN-γ enhances the immune response of macrophages against M. marinum infection. On the other hand, the anti-inflammatory cytokine showed a delayed increase, significantly reducing the expression of pro-inflammatory cytokines. The expression of both cytokines balanced each other and together regulated the inflammatory reaction against M. marinum infection.
研究领域:
免疫学
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微生物学
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分子生物学
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细胞生物学
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Huijuan Ma,Tingqian Wang,Junfeng Wang,Peiyao Wang,Qi Shu,Ruilin Qin,Sijia Li,Huan Xu
The correlation between formaldehyde (FA) exposure and prevalence of asthma has been widely reported. However, the underlying mechanism is still not fully understood. FA exposure at 2.0 mg/m 3 was found to exacerbate asthma in OVA-induced murine models. IFN-γ, the cytokine produced by T helper 1 (Th1) cells, was significantly induced by FA in serum and bronchoalveolar lavage fluid (BALF) of asthmatic mice, which was different from cytokines secreted by other Th cells. The observation was also confirmed by mRNA levels of Th marker genes in CD4+ T cells isolated from BALF. In addition, increased production of IFN-γ and expression of T-bet in Jurkat T cells primed with phorbol ester and phytohaemagglutinin were also observed with 100 μM FA treatment in vitro . Upregulated STAT1 phosphorylation, T-bet expression and IFN-γ production induced by FA was found to be restrained by STAT1 inhibitor fludarabine, indicating that FA promoted Th1 commitment through the autocrine IFN-γ/STAT1/T-bet pathway in asthma. This work not only revealed that FA could bias Th lineage commitment to exacerbate allergic asthma, but also identified the signaling mechanism of FA-induced Th1 differentiation, which may be utilized as the target for development of interfering strategies against FA-induced immune disorders.
研究领域:
免疫学
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呼吸病学
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毒理学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Xianghong Wang,Rong Lin,Dehai Li,Weiyuan Ye,Zhe Yang,Niujian Wu,Qiong Wen,Jingyi Tan,Chuanchuan Sun,Zhinan Yin,Hongyun Lu,Hengwen Yang
Previous studies have established that γδ T cells play a significant role in liver fibrosis. However, their specific functions and mechanisms in fibrotic liver tissue remain unclear. Using online microarray expression profiles, we observed that USF3 was upregulated in patients with liver fibrosis and was associated with immune cells. Additionally, increases in the expression of USF3 correlated with elevated levels of interferon-gamma (IFN-γ) in γδ T cells. However, the regulatory impact of USF3 on T cells, particularly in relation to fibrosis, has not been sufficiently elucidated. In this study, we employed conditional knockout mice (USF3 f/f ; CD2-cre) to investigate the role of USF3 in γδ T cells. The conditional knockout of USF3 resulted in an increase in both the number and proliferation of γδ T cells, which was associated with mTOR signaling pathway activation. The absence of USF3 significantly enhanced the expression of Eomes in γδ T cells, leading to an increase in IFN-γ production. Importantly, liver fibrosis was alleviated in USF3 conditional knockout mice, which was potentially linked to the enhanced proliferation of γδ T cells and the elevated expression of cytotoxic molecules, including IFN-γ. In summary, targeting USF3 in γδ T cells may represent a promising immunotherapeutic approach for liver fibrosis.
研究领域:
免疫学
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肝脏病学
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分子生物学
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2022
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IF 12.545
Yanli Zhou,Jiaxiang Liu,Hui Dong,Zi Liu,Lu Wang,Qiaoxia Li,Jianhua Ren,Yintang Zhang,Maotian Xu
Interferon-gamma (IFN- γ ) is one kind of crucial inflammatory cytokines, and its expression level is closely associated with various disease progressions. This work addresses the development of a sensitive and specific electrochemical assay for detection of IFN- γ by combing the recognition unit of aptamer with the signal reporter of target-induced silver nanoclusters (AgNCs). For biosensor preparation, the gold nanoparticles (AuNPs) immobilized on the amine-terminated electrode surface provided electrochemical interfaces for the self-assembly of C-rich modified aptamers. Then, the aptamer recognized IFN- γ and the free aptamer hybridized with conjugated DNA sequences . After the nuclease-catalyzed cleavage of DNA duplex, in situ-generated AgNCs in the C-rich template was utilized as the electrochemical indicator for IFN- γ detection. The present method demonstrated a good performance for detection of IFN- γ with a low detection limit of 1.7 pg mL −1 . This aptasensor was verified to be applied for the evaluation of IFN- γ secreted by cell.
研究领域:
生物化学
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分析化学
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纳米技术
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免疫学
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2026
·Vol. 51
·期 4
·232
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IF 4.5
Zhang Xinfeng,Lian Zhuo,Lei Sijie,Yi Tanhui,Zhao Shuyin,Liu Mingxiang,Gui Yiling,Zhu Chengyi,Xie Qian,Ma Rong
The selection of appropriate in vitro inflammatory models is critical for mechanistic studies of neuroinflammation and the screening of anti-inflammatory therapeutics. Lipopolysaccharide (LPS) combined with interferon-γ (IFN-γ) and LPS combined with adenosine triphosphate (ATP) are widely used to induce microglial inflammation; however, their distinct phenotypic characteristics and optimal applications have not been systematically compared. In this study, we combined transcriptomic profiling with functional assays to compare these two inflammatory paradigms in BV2 microglia. Our results showed that both models activated the chemokine–cytokine inflammatory network and induced the production of inflammatory mediators and chemokines, but exhibited distinct molecular and functional biases. LPS/IFN-γ stimulation preferentially upregulated genes such as Lcn2 , Ccl2 , Upp1 , and Pim2 , which are associated with innate immune activation, chemokine-mediated inflammatory responses, and cell survival signaling, and was accompanied by marked increases in NO and TNF-α production. In contrast, the LPS/ATP model preferentially upregulated genes associated with ECM/cell adhesion, inflammatory and cellular homeostatic regulation, oxidative stress, and calcium-dependent secretion, including Thbs1 , Thbd , Srxn1 , Syt7 , and Procr . Functionally, this model exhibited more pronounced IL-1β maturation and release, relatively lower NO production, and greater mitochondrial dysfunction and cell injury. Pharmacological inhibition of NLRP3 with MCC950 significantly attenuated ATP-induced IL-1β maturation, supporting the involvement of the NLRP3 inflammasome in the LPS/ATP model. Overall, the LPS/IFN-γ model is more suitable for investigating the NO/iNOS–TNF-α axis, IFN-γ-mediated synergistic pro-inflammatory responses, and classical pro-inflammatory activation, as well as for screening anti-inflammatory agents. In contrast, the LPS/ATP model is more appropriate for studying IL-1β maturation and release, NLRP3 inflammasome activation, mitochondrial damage, and inflammation-related cell death, as well as for screening inflammasome inhibitors. Our findings provide an empirical framework for rational model selection in microglial inflammation research.
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Jian Xiao,Nana Feng,Qiushi Li,Xianghui Cao,Qingqing Huang,Biyu Zhou,Zhenrui Fan,Liping Wei,Yang Liu
Ferroptosis is gaining attention as a potential cancer immunotherapy strategy, as it can stimulate antitumor responses by enhancing dendritic cell (DC) activation and the infiltration of cytotoxic T cells (CTLs). However, cancer cells often develop resistance to ferroptosis, reducing the effectiveness of existing treatments. This study demonstrates a novel mitochondria-targeted ferroptosis inducer, designated mitoFePDA@R, which is engineered to achieve a “closed-loop” cancer immunotherapy strategy of ferroptosis induction, antitumor immune activation, and ferroptosis enhancement. In this strategy, mitoFePDA@R is designed to release Fe 2+ and the mitoGPX4 inhibitor RSL3 within tumor mitochondria, thereby effectively inducing ferroptosis and activating strong antitumor immune responses. Additionally, interferon γ ( IFN-γ) released from CTLs inhibits GSH synthesis, which further enhances the ferroptosis sensitivity of tumor cells to form a “closed-loop” strategy. In vitro studies indicated that mitoFePDA@R induced strong ferroptosis in tumor cells by accumulating lipid peroxides (LPO) in mitochondria (which lacks mitochondria targeting). Animal studies confirmed that mitoFePDA@R effectively triggered ferroptosis and activated subsequent antitumor immune responses, leading to significant tumor growth inhibition. This provides a viable and effective strategy for ferroptosis-associated cancer immunotherapy.
研究领域:
肿瘤学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
EXPERIMENTAL DERMATOLOGY
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2019
·Vol. 28
·期 11
·1227-1236
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IF 2.868
Fei Yi,Xiaoli Zheng,Fang Fang,Jiaan Zhang,Bingrong Zhou,Xiangsheng Chen
Background Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is a well-known treatment for non-hypertrophic actinic keratoses and superficial basal-cell carcinomas. Objectives In this study, we first revealed that ALA-PDT treatment effectively ameliorated the psoriasis-like lesion in imiquimod (IMQ)-induced mouse model and further explored the potential molecular mechanism and related signalling pathways during the treatment. Besides, we also confirmed a significant alleviation of ALA-PDT therapy on IFN-γ-induced over-proliferation of keratinocytes. Methods H&E staining was conducted to reveal the histological changes of mice in different groups. The different expression levels of RNA were illustrated by using QRT-PCR. Western blot was performed to confirm the various expression levels of protein in mice. In vitro, cell proliferation and cell cycle were evaluated by cell counting kit-8 and flow cytometry assay, respectively. Results The result showed that ALA-PDT’s anti-proliferation effect and regulation on Socs1 /3, JAK1 /2 and K17 in IFN-γ-induced keratinocytes were largely weakened by NAC, indicating that ALA-PDT attenuated the proliferation of IFN-γ-induced keratinocytes by enhancing ROS level. Conclusions These results demonstrated that ALA-PDT largely activated the productivity of Socs1 /3 in a ROS-dependent manner. Socs1 /3 is a potential blocker in JAK signalling pathway and inhibits the proliferation and keratinization of keratinocytes in psoriasis.
研究领域:
皮肤科
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分子生物学
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光动力疗法
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Jing Yang,Zhu Liang,Hui Zhao,Jingping Huang,Ying Song,Jingyu Zhu,Yishu Yan,Yuntao Zhu
IFN-γ has been shown to exert potent anti-fibrotic effects in early stages of liver fibrosis, but the drug development has been impeded by systemic toxicity arising from off-target receptor activation. To overcome this therapeutic challenge, a nanodelivery platform (~200 nm) through covalent conjugation of sulfated hyaluronan (S-HA) with branched polyethyleneimine (PEI) was developed. Upon loading with IFN-γ, the nanoplatform achieved significantly enhanced hepatic accumulation effect. The resulting S-HA-PEI-IFN-γ formulation significantly attenuated M1 type macrophage polarization and associated pro-inflammatory cytokine release induced by free IFN-γ treatment, the key contributors to systemic adverse effects. Mechanistically, the nanoparticle of S-HA-PEI within the formulation exhibited synergistic effect with IFN-γ to suppress hepatic stellate cell (HSC) activation by blocking TGF-β/Smads signaling pathway. In a CCl 4 -induced murine liver fibrosis model, S-HA-PEI-IFN-γ administration achieved remarkable reduction in collagen deposition as compared to free IFN-γ treatment, accompanied by concurrent downregulation of Collagen-I (Col I) and α-smooth muscle actin (α-SMA) expression. By integrating targeted delivery, toxicity mitigation and synergistic anti-fibrotic effect, the S-HA-PEI-IFN-γ nano-therapeutic represents a promising transformative strategy for combating liver fibrosis.
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PubMed
高影响因子
Materials Today Nano
·
2024
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IF 8.2
Hao Wang,Siyu Hou,Weihao Feng,Dongliang Li,Jialin Liu,Weisong Yang,Suichu Huang,Feiran Li,Xuezeng Zhao,Fang Chen,Cong Huang,Yunlu Pan
Biosensors based on field-effect transistor (FET) are extensively utilized in biomedical engineering for their capability to achieve rapid and label-free detection of targets. However, the extremely low concentration level of biomarkers, crucial for human health, put forward higher requirements for biosensors. Developing stable and reliable biosensors with high sensitivity for biomarker detection remains challenging. In this study, we report a highly sensitive MoS 2 -FET biosensor for the cytokine IFN-γ. Surface etching of the MoS 2 channel using a reactive ion etching system increases reactive sites for biological molecules on the channel surface, thereby enhancing the detection performance of the biosensor. The MoS 2 -FET biosensor functionalized with aptamer demonstrates high sensitivity and selectivity for IFN-γ detection (limit of detection is 5.98×10 -5 nM). Notably, the signal responses of the MoS 2 -FET biosensor are higher than that of the MoS 2 -FET biosensor without Ar etching and graphene-FET biosensor. Additionally, this paper analyzes the relationship between the modification density of probe molecules and the biosensor's detection signal, establishing a theoretical foundation for further enhancing the sensor's detection performance. Experimental results confirm that the highly sensitive MoS 2 -FET biosensor provides an effective testing platform for the biomarkers with low concentrations, crucial for disease prevention and early diagnosis.
研究领域:
生物医学工程
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纳米技术
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DOI
高影响因子
危险品化学品经营许可证（带存储）