1.Effects of IL-17A on fibrosis of skin and lung in a mouse model of systemic sclerosis
Shuning HUANG ; Ling LEI ; Cheng ZHAO ; Xu WANG ; Jing WEN ; Fang QIN
Chinese Journal of Microbiology and Immunology 2017;37(2):105-111
Objective To analyze the expression of interleukin ( IL)-17A in a mouse model of bleomycin ( BLM)-induced systemic sclerosis ( SSc) and to evaluate its effects on inflammation and fibrosis in skin and lung tissues. Methods Twenty-four female BALB/c mice were randomly divided into four groups:normal control group ( mice were subcutaneously injected with phosphate buffer ) , model group (subcutaneously injected with BLM), antibody group (injected with BLM + IL-17A monoclonal antibody), homotypic control group ( injected with BLM + isotype control) . Pathological changes in skin and lung tis-sues of those mice were observed;inflammatory and fibrotic scores were assessed. Immunohistochemistry and real-time fluorescent quantitative PCR ( RT-PCR) were used to detect the expression of IL-17A, TGF-β1 and typeⅠ collagen in skin and lung tissues of those mice at mRNA level. Mouse lung fibroblasts ( FB) de-rived from the mice of model group were cultured in vitro and then were cultured with IL-17A cytokines with or without the interference of monoclonal antibodies. Expression of typeⅠ collagen and TGF-β1 at mRNA level and levels of IL-6 and TGF-β1 in the culture supernatants were detected by RT-PCR and enzyme-linkedimmunosorbent assay ( ELISA) , respectively. Results Compared with the mice of model and homotypic control groups, those of the antibody group showed mild skin thickening, skin inflammation and lung inflam-mation as well as lower fibrosis scores (P<0. 05). The expression of IL-17A at both protein and mRNA lev-els and the expression of TGF-β1 and collagen typeⅠat mRNA level in skin and lung tissues of mice of the antibody group were significantly lower than those of the model and homotypic control group (P<0. 05). Re-sults of the in vitro cell culture of SSc mice-derived lung FB with IL-17A showed that the expression of TGF-β1 and typeⅠ collagen at mRNA level and the levels of IL-6 and TGF-β1 in the culture supernatants were decreased with the interference of anti-IL-17A monoclonal antibody (P<0. 05), but were still higher than those of the control group (P<0. 05). Conclusion IL-17A promotes the development of inflammation and fibrosis in skin and lung tissues in the mouse model of SSc. Blocking IL-17A might inhibit fibrosis in SSc by inhibiting the production of TGF-β1, IL-6 and typeⅠ collagen.
2.Ultrasmall iron-quercetin metal natural product nanocomplex with antioxidant and macrophage regulation in rheumatoid arthritis.
Zhihui HAN ; Xiang GAO ; Yuanjie WANG ; Shuning CHENG ; Xiaoyan ZHONG ; Yong XU ; Xiaozhong ZHOU ; Zengli ZHANG ; Zhuang LIU ; Liang CHENG
Acta Pharmaceutica Sinica B 2023;13(4):1726-1739
Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.