inflammatory damage
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2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Yun Yang ◽  
Xiu-Ming Li ◽  
Jing-Ru Wang ◽  
Yan Li ◽  
Wen-Long Ye ◽  
...  

Abstract Background TRIP6 is a zyxin family member that serves as an adaptor protein to regulate diverse biological processes. In prior reports, TRIP6 was shown to play a role in regulating inflammation. However, its in vivo roles and mechanistic importance in colitis remain largely elusive. Herein, we therefore employed TRIP6-deficient (TRIP6−/−) mice in order to explore the mechanistic importance of TRIP6 in a dextran sodium sulfate (DSS)-induced model of murine colitis. Findings Wild-type (TRIP6+/+) mice developed more severe colitis following DSS-mediated disease induction relative to TRIP6−/− mice, as evidenced by more severe colonic inflammation and associated crypt damage. TRIP6 expression in wild-type mice was significantly elevated following DSS treatment. Mechanistically, TRIP6 binds to TRAF6 and enhances oligomerization and autoubiquitination of TRAF6. This leads to the activation of NF-κB signaling and the expression of pro-inflammatory cytokines such as TNFα and IL-6, in the in vivo mouse model of colitis. Conclusions These in vivo data demonstrate that TRIP6 serves as a positive regulator of DSS-induced colitis through interactions with TRAF6 resulting in the activation of inflammatory TRAF6 signaling, highlighting its therapeutic promise as a protein that theoretically can be targeted to prevent or treat colitis.


2022 ◽  
Vol 12 ◽  
Author(s):  
Lu Xia ◽  
Yu Liu ◽  
Zhiwei Zhang ◽  
Yajuan Gong ◽  
Tianyi Yu ◽  
...  

Interleukin-6 (IL-6) overproduction has been considered to contribute to inflammatory damage of glomerular mesangial cells (GMCs) in human mesangial proliferative glomerulonephritis (MsPGN) and its rat model called Thy-1 nephritis (Thy-1N). However, the regulatory mechanisms of IL-6 expression in GMCs upon sublytic C5b-9 timulation remain poorly understood. We found that Krüppel-like factor 4 (KLF4) bound to the IL-6 promoter (−618 to −126 nt) and activated IL-6 gene transcription. Furthermore, lysine residue 224 of KLF4 was acetylated by p300/CBP-associated factor (PCAF), which was important for KLF4-mediated transactivation. Moreover, lysine residue 5 on histone H2B and lysine residue 9 on histone H3 at the IL-6 promoter were also acetylated by PCAF, which resulted in an increase in IL-6 transcription. Besides, NF-κB activation promoted IL-6 expression by elevating the expression of PCAF. Overall, these findings suggest that sublytic C5b-9-induced the expression of IL-6 involves KLF4-mediated transactivation, PCAF-mediated acetylation of KLF4 and histones, and NF-κB activation in GMCs.


2021 ◽  
Vol 12 (3) ◽  
pp. 045-056
Author(s):  
Kedar N Prasad

The major eye diseases refractive error, cataract, age-related macular degeneration (ARMD), glaucoma, and diabetic retinopathy can lead to blindness without an early intervention. The treatments include eye glasses for refractive error, surgery for cataract, and medications for glaucoma and ARMD. These therapies do not address oxidative stress and inflammation that contribute to these eye diseases. Therefore, supplementation with antioxidants could be useful. However, administration with single or multiple dietary antioxidants with or without carotenoids (zeaxanthin and lutein), and omega-3-fatty acids, produced no benefits or only modest benefits in certain eye diseases. The problems associated with such antioxidant’s approaches were identified, and potential causes for not producing optimal benefits were presented. The major objectives are to show that enhanced oxidative stress and inflammation contribute to the age-related major eye diseases. This review presents rationales for using a comprehensive mixture of micronutrients containing dietary and endogenous antioxidants, vitamin D3, and carotenoids such as lutein, zeaxanthin, astaxanthin, all B-vitamins, and minerals Zn and Se for simultaneously reducing oxidative and inflammatory damage. Since elevated levels of vascular endothelial growth factor (VEGF) are found in the wet ARMD and diabetic retinopathy, this mixture has ingredients, which reduce VEGF levels. Supplementation with this micronutrient mixture may delay the onset and progression of major eye diseases, and may improve the effectiveness of standard therapy.


Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7656
Author(s):  
Yang Chen ◽  
Yaoyun Niu ◽  
Wenhui Hao ◽  
Wanqiu Zhang ◽  
Jinghua Lu ◽  
...  

Colitis is not fully curable, although currently, some treatment options are being adopted. In this study, we investigated the effects of pineapple leaf phenols (PLPs), natural phenol products from pineapple leaves, on DSS-induced colitis in mice. The results showed that PLPs dramatically decreased the inflammatory response by inhibiting NF-κB activation and the secretion of pro-inflammatory factors. Moreover, PLPs provided protection against DSS-induced acute colitis by maintaining epithelial integrity. Caffeic and P-coumaric acids had similar effects and could be the active components responsible for PLPs’ effect on colitis. These results indicate that the oral administration of PLPs might be considered as a therapeutic strategy in the treatment of patients with colitis. However, further research on clinical applications and the exact effect of PLPs on colitis is required.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hanfen Tang ◽  
Ming Yang ◽  
Yinghong Liu ◽  
Hong Liu ◽  
Lin Sun ◽  
...  

Diabetic nephropathy (DN) is one of the most severe complications of diabetes. Inflammation mediated by inflammatory factors is thought to accelerate the progression of renal damage in DN. However, which inflammatory factors mediate the inflammatory response in DN remains unclear. In this study, we determined that the CXCL1-mediated inflammatory response may play an essential role in DN progression through bioassays. Subsequently, we observed that the expression of CXCL1 and its receptor (CXCR2) was significantly increased in the kidneys of mice with HFD + STZ induced diabetes and DN patients. In addition, inhibition of the CXCL1/CXCR2 axis by repertaxin alleviates renal inflammation and pathological damage in the kidneys of db/db mice. Finally, we noted that the CXCL1/CXCR2 axis might lead to inflammatory damage through phosphorylated NF-κB and further activate the NLRP3 inflammasome. Our results revealed the role of the CXCL1/CXCR2 axis in DN progression for the first time, which may be a novel therapeutic target for DN.


2021 ◽  
Vol 225 ◽  
pp. 112730
Author(s):  
Youjing Yang ◽  
Shuhui Wei ◽  
Kaimiao Chu ◽  
Qianmin Li ◽  
Yujia Zhou ◽  
...  

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 1041-1041
Author(s):  
Michael Borack ◽  
Kathryn Porter Starr ◽  
Connie Bales ◽  
Jamie Rincker ◽  
Lou DeFrate ◽  
...  

Abstract Age-related increases in chronic inflammation lead to reduced physical function via damage to muscle and joints and contribute to osteoarthritis (OA) risk. Obesity in older adults with OA further exacerbates inflammatory damage. Whether obesity reduction can lessen inflammation and improve OA is unknown; however, novel biomarkers may provide an answer. We completed a 6-mo. weight loss intervention (-500 kcal/day), studying blood biomarkers of inflammation and cartilage damage along with physical function in obese older adults with (OA+; n=39) and without an OA diagnosis (OA-; n=20). Participants were aged > 60 yrs (mean = 70.2±6.0) and obese (BMI =34.6±4.7 kg/m2). At endpoint, weight loss was -6.3±4.0% and -5.8±4.1% in OA+ and OA-, respectively, with no group difference. Change scores for function for OA+ and OA- were: Short Physical Performance Battery score (+1.7±1.3 and +2.1±1.5), 8 ft up and go (-0.7±1.0 and -0.9±1.12 sec) and 6 min walk (+31.4±105.1 and +39.5±57.4 meters). All improved from baseline (p<0.05), with no group difference. Concerning blood biomarkers, there was a decrease (p<0.05) in cartilage oligomeric matrix protein (COMP: OA biomarker), indicating a potential benefit for OA. Change in COMP also differed between groups; OA- had a greater (p<0.05) reduction than OA+. Pooled results showed improved adiponectin (p<0.05), with no group difference. There were no changes for CRP, CTX-1, IL-6 and TNF-α. Our novel findings link early intervention with better reduction of OA risk and inflammation in obese older adults and also show important benefits for improved physical function regardless of OA status.


2021 ◽  
Author(s):  
Xue Bai ◽  
Hongyan Sun ◽  
Lina Jia ◽  
Junjie Xu ◽  
Peng Zhang ◽  
...  

Abstract Background: Cartilage destruction caused by inflammation is a clinical challenge. Many studies have investigated cartilage destruction in adults, but little research was conducted on children. Results: The gaps without chondrocytes and ECM between the proliferative and hypertrophy zones of the GP cartilage were formation after the treatment of LPS, but the gaps were not observed in the AuNPs + LPS group. This finding can be attributed to the capability of AuNPs to target to the chondrocytes and reduce the release of inflammatory cytokines and secretion of ECM degradation factors induced by LPS. And then, the LPS-induced apoptosis rate of mouse chondrocytes and ECM degradation rate were inhibited. Finally, the balance of catabolic and anabolic factors in the ECM was maintained.Conclusion: These findings indicate that AuNPs can partially protect the cartilage of children from inflammatory damage by suppressing chondrocyte apoptosis and ECM degradation.


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