Pristane induces autophagy in macrophages, promoting a STAT1-IRF1-TLR3 pathway and arthritis

Zhu, Wenhua; Xu, Jing; Jiang, Congshan; Wang, Bo; Geng, Manman; Wu, Xiaoying; Hussain, N.; Gao, Ning; Han, Yong; Li, Dongmin; Lan, Xi; Ning, Qilan; Zhang, Fujun; Holmdahl, Rikard; Meng, Liesu; Lu, Shemin

doi:10.1016/j.clim.2016.11.017

Cited by 17 publications

(17 citation statements)

References 48 publications

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“…In this case, the mean of the joint spaces of both groups are not significantly different (P>0.05). It is predicted that the autophagy mechanism which is stated by Zhu [13] occurs, so the joint disorder develops without the equal increase of total IL-6. It might be a result of upregulation of TLR 3 on macrophages [16] causes the control of marker cells in rheumatoid diseases [17].…”

Section: Resultsmentioning

confidence: 98%

“…In contrary, the lupus patients do not experience excessive inflammation except the local joint inflammation when the flaring period happens. Deretic [12] and Zhu [13] explain the phenomenon that TMPD could lead to autophagy of the macrophages in vitro and in vivo in the spleen. There is no clear information about the impact of the autophagy on the innate and adaptive immune system.…”

Section: Introductionmentioning

confidence: 99%

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The Role Of IL-6 In TMPD-Treated Lupus Arthritis Mice

Indriyanti

2017

KLS

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Lupus or systemic lupus erythematosus is a chronic autoimmune disease with systemic inflammation manifestations mainly in targeted organs. The appropriate animal model for lupus is necessary. The induction method by using 2,6,10,14 tetramethylpentadecane (TMPD) reveals more complex manifestations than other hydrocarbons. However, the autophagy of macrophages as an effect of TMPD makes differences to make the decision in lupus biomarker as a targeted therapy in lupus arthritis. Thus, this research focused on the role of CD68+IL-6 produced by macrophages and total IL-6 in lupus in correlation to the arthritis severity. The naïve and TMPD-treated groups (n=3) were induced by means of 0.5 ml TMPD i.p.After 6 months, the mice were sacrificed then the fresh spleens were prepared as isolated cells to be measured by using flow cytometry method. The knee joints were prepared for histology observation. The statistical analysis was performed by using T-test SPSS 22 version. The results showed the relative percentage of CD68+IL-6+ in the TMPD-treated group increased significantly (P<0.05) with the value of 62.38±9.97 %, compared to naïve group 49.70±2.34 %. Moreover, the total IL-6 did not increase significantly (P>0.05). Meanwhile, the arthritis severity score of the TMPD-treated group revealed severe erosion with the grade of 3.7±1.06, higher significantly (P<0.05) than the naïve group (0.5±0.71). The joint spaces in both groups were not significantly different. Finally, the observations gave the clear information that despite the autophagy potency, the CD68+IL-6 and the arthritis severity score were good markers in lupus preclinical study.

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Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

The Role Of IL-6 In TMPD-Treated Lupus Arthritis Mice

Indriyanti

2017

KLS

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“…There are a wide variety of lupus-specific antibodies. 8 A lupus drug candidate is highly potential if it reduces anti-Smith (anti-Sm) antibody, which is the main antibody that affects the tyrosine kinase. 9 Therefore, anti-Sm trigs the production of a lot of lupus-specific antibodies.…”

Section: Resultsmentioning

confidence: 99%

FOXP3 Modulation of Quercetin-3-O-rhamnoside and its Impacts on Lupus Nephritis Mice

Indriyanti¹,

Soeroso²,

Khotib³

2018

JYP

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Background: Quercetin-3-O-rhamnoside (QUE) has anti-inflammatory and anti-oxidative effects which probably beneficially used in lupus. Objective: This research was focused on analyzing the effects of QUE on FOXP3 modulation to result in an anti-inflammatory outcome in the kidney of severe lupus mice. Methods: This research used Pristane-induced female BALB/c lupus mice, and the biomarkers involved in were CD4 + CD25+ T reg cells, FOXP3 T cells, anti-Sm, IL-6, and histopathology assessment of the kidney of lupus mice. The QUE group was treated and compared to the negative control which received placebo, and the positive control which received cyclophosphamide. Results: QUE increased the number of CD4 + CD25 + T reg cells (negative control: 3.01±3.43%; QUE: 18.77±5.12%; positive control: 3.26±11.09%), and FOXP3 significantly (p<0.05) (negative control: 1.14±0.54%; QUE: 2.00±1.45%; positive control: 1.73±1.14%). The antiSm level did not decrease, meanwhile the IL-6 decreased significantly, and the histopathological assessment of the kidney reveal the repairing effects of QUE on glomeruli. Conclusion: QUE has an anti-inflammatory activity which reduces the severity of lupus nephritis signs in lupus mice by initially increasing the CD4 + CD25+ and FOXP3 + Tregs numbers. QUE is potential to be further developed as a safe treatment choice for lupus nephritis. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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“…The mice aged 7 weeks when induced using TMPD. The positive lupus mice were obtained after 6 months [26,27]. The lupus mice were divided into 3 experimental groups (10 mice per group).…”

Section: The Lupus Mice Preparationmentioning

confidence: 99%

“…It has been known that macrophages mainly used in the innate immune response, whether the T-cells act in adaptive immune response [34]. The macrophage autophagy in lupus is one cause that might be considered as the leading caution of the insignificant IL-6 decrease [27,35]. It seems logical since the passive lupus manifestation still reveals the organ disorder, without severe inflammations occur.…”

Section: Il-6mentioning

confidence: 99%

The Benefits of Active Compounds in Kalanchoe Pinnata (Lmk) Pers Ethyl Acetate Fraction on Lupus Arthritis Mice

Indriyanti

Soeroso

Khotib

2017

Asian J Pharm Clin Res

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Objective: The aim of this research was to measure the effects of the ethyl acetate fraction of Kalanchoe pinnata (Lmk) Pers (EF-KP) on lupus arthritis mice. Methods:The research was performed by testing of CD123 + interferon-α (IFN-α + ) dendritic cells and CD68 + interleukin 6 (IL-6 + ) macrophages as the main biomarkers using flow cytometry method, and then, the outcomes were directly observed in the joint's tissue structure. The results of the research were analyzed using statistics. Results IL-6+ macrophages but not significantly. Finally, the outcome to the grade of joint damage was scored using Pritzker method. The treated groups have one grade lower, and the joint spaces were narrower than the untreated group. Conclusion:The results show the ability of the active compounds in EF-KP, which are comparable to 0.042 mg/kg of quercetin, to inhibit the progress of lupus arthritis pathogenesis in mice. It might reveals the effectiveness of the EF-KP in human with lupus arthritis. However, the further clinical research is necessary.

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Pristane induces autophagy in macrophages, promoting a STAT1-IRF1-TLR3 pathway and arthritis

Cited by 17 publications

References 48 publications

The Role Of IL-6 In TMPD-Treated Lupus Arthritis Mice

The Role Of IL-6 In TMPD-Treated Lupus Arthritis Mice

FOXP3 Modulation of Quercetin-3-O-rhamnoside and its Impacts on Lupus Nephritis Mice

The Benefits of Active Compounds in Kalanchoe Pinnata (Lmk) Pers Ethyl Acetate Fraction on Lupus Arthritis Mice

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