Interleukin-12p35 deficiency enhances mitochondrial dysfunction and aggravates cardiac remodeling in aging mice

Ye, Jing; Wang, Yuan; Wang, Zhen; Liu, Ling; Yang, Zicong; Ye, Di; Wang, Menglong; Xu, Yao; Zhang, Jishou; Zhao, Mengmeng; Liu, Jianfang; Lin, Yingzhong; Ji, Qingwei; Wan, Jun

doi:10.18632/aging.102609

Cited by 18 publications

(16 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Antibodies against IL-22 (GeneTex), IL-10R2 (Abcam), IL-22R1 (Santa Cruz), Bax, Bcl2, cleaved caspase-3, extracellular regulated protein kinase (ERK), p-ERK, p38, p-p38, c-Jun N-terminal kinase (JNK), p-JNK, signal transducer and activator of transcription (STAT) 3, p-STAT3, and STAT1 were purchased from Cell Signaling Technology, and antibodies against p-STAT1, STAT5, p-STAT5, p65, and p-p65 were purchased from Abcam. The western blotting was performed according to the methods described in our previous articles [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

Interleukin-22 deficiency alleviates doxorubicin-induced oxidative stress and cardiac injury via the p38 MAPK/macrophage/Fizz3 axis in mice

Wang

et al. 2020

Redox Biology

Self Cite

View full text Add to dashboard Cite

Several interleukin (IL) family members have been demonstrated to be involved in doxorubicin (DOX)-induced cardiac injury. This study aimed to investigate the role of IL-22 in DOX-induced cardiac injury and explore its possible mechanisms. In this study, mice were given DOX, and the cardiac expression and sources of IL-22 were determined. Then, IL-22 was knocked out to observe the effects on DOX-induced cardiac injury in mice. In addition, the p38 mitogen-activated protein kinase (MAPK) pathway was inhibited, macrophages were depleted and adoptively transferred, and Fizz3 was up-regulated in mice to explore the mechanisms. The results showed that cardiac IL-22 expression was significantly increased by DOX treatment and was mostly derived from cardiac macrophages. IL-22 knockout significantly reduced cardiac vacuolization and the expression of cardiomyocyte injury markers in both serum and left ventricular tissue and improved cardiac function in DOX-treated mice. In addition, IL-22 knockout reversed DOX-induced cardiac M1 macrophage/M2 macrophage imbalance, reduced oxidative stress and protected against cardiomyocyte apoptosis. p38 MAPK pathway inhibition with SB203580 and macrophage depletion further alleviated the above effects in DOX-treated IL-22-knockout mice. The effects were stronger IL-22-knockout mice with adoptive transfer of WT macrophages than in those with adoptive transfer of IL-22-knockout macrophages. Furthermore, increasing the expression of Fizz3 reduced cardiomyocyte apoptosis and alleviated cardiac dysfunction. Our results may suggest that IL-22 knockout alleviate DOX-induced oxidative stress and cardiac injury by inhibiting macrophage differentiation and thereby increasing the expression of Fizz3. Reductions in IL-22 expression may be beneficial for clinical chemotherapy in tumor patients.

show abstract

Section: Methodsmentioning

confidence: 99%

Interleukin-22 deficiency alleviates doxorubicin-induced oxidative stress and cardiac injury via the p38 MAPK/macrophage/Fizz3 axis in mice

Wang

et al. 2020

Redox Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Unexpectedly, Yan et al also reported that IL-23 deficiency amplifies the inflammatory response and promotes the release of various inflammatory factors, especially IL-17, which further promotes the infiltration and deposition of gdT cells in the left ventricle, promotes the apoptosis of cardiomyocytes, and aggravates cardiac fibrosis in a murine myocardial infarction model . In addition, IL-12p35 knockout increased the levels of cardiac mitochondrial reactive oxygen species (ROS) and calcium ion overload, which further aggravated mitochondrial dysfunction and energy failure, increased myocardial cell apoptosis, worsened cardiac dysfunction, and increased cardiac fibrosis in 25-month-old aging mice (Ye et al, 2020). However, how the cytokines IL-12 and IL-35 mediate these biological effects is currently unknown.…”

Section: Interleukin-12 Family Members and Cardiac Fibrosismentioning

confidence: 99%

Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges

Wang

et al. 2020

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Cardiovascular diseases represent a complex group of clinical syndromes caused by a variety of interacting pathological factors. They include the most extensive disease population and rank first in all-cause mortality worldwide. Accumulating evidence demonstrates that cytokines play critical roles in the presence and development of cardiovascular diseases. Interleukin-12 family members, including IL-12, IL-23, IL-27 and IL-35, are a class of cytokines that regulate a variety of biological effects; they are closely related to the progression of various cardiovascular diseases, including atherosclerosis, hypertension, aortic dissection, cardiac hypertrophy, myocardial infarction, and acute cardiac injury. This paper mainly discusses the role of IL-12 family members in cardiovascular diseases, and the molecular and cellular mechanisms potentially involved in their action in order to identify possible intervention targets for the prevention and clinical treatment of cardiovascular diseases.

show abstract

“…However, reducing cardiomyocyte apoptosis can significantly reverse cardiac dysfunction, suggesting that sepsis-induced excessive apoptosis of cardiomyocytes might be the most fundamental cause of cardiac injury [ 36 ]. AIF, which exists mainly in the mitochondrial inner membrane and is less prevalent or nonexistent in the nucleus, is one of the important factors mediating non-Caspase-dependent apoptosis [ 22 ]. Under stimulation by external pathological factors, AIF is released in massive quantities by mitochondria and transferred to the nucleus through the cytoplasm [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondria were isolated from the left ventricle (LV) using a mitochondrial isolation kit (Cayman) as described in our previous study [ 22 ]. In brief, fresh LV tissue was lysed using a mitochondrial separation solution and then centrifuged at 700 × g for 10 minutes.…”

Section: Experimental Materials and Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Anti‐Interleukin‐16 Neutralizing Antibody Treatment Alleviates Sepsis‐Induced Cardiac Injury and Dysfunction via the Nuclear Factor Erythroid‐2 Related Factor 2 Pathway in Mice

Zhang

Yang

Liang

et al. 2021

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Several interleukin (IL) members have been reported to participate in sepsis. In this study, the effects of IL-16 on sepsis-induced cardiac injury and dysfunction were examined, and the related mechanisms were detected. IL-16 expression in septic mice was first measured, and the results showed that both cardiac and serum IL-16 expression levels were increased in mice with sepsis induced by LPS or cecal ligation and puncture (CLP) compared with control mice. Then, IL-16 was neutralized, and the effects on lipopolysaccharide- (LPS-) induced cardiac injury were detected. The results showed that an anti-IL-16 neutralizing antibody (nAb) significantly reduced mortality and increased serum lactate dehydrogenase (LDH), creatine kinase myocardial bound (CK-MB), and cardiac troponin T (cTnT) levels while improving cardiac function in mice with LPS-induced sepsis. Neutralization of IL-16 also increased the activation of antioxidant pathways and the expression of antioxidant factors in septic mice while decreasing the activation of prooxidant pathways and the expression of prooxidants. Treatment with the anti-IL-16 nAb increased mitochondrial apoptosis-inducing factor (AIF) expression, decreased nuclear AIF and cleaved poly-ADP-ribose polymerase (PARP) expression, and decreased TUNEL-positive cell percentages in LPS-treated mice. Additionally, treatment with CPUY192018, the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway, significantly increased mortality and reversed the above effects in mice treated with LPS and the anti-IL-16 nAb. Our results showed that the anti-IL-16 nAb regulates oxidative stress through the Nrf2 pathway and participates in the regulation of cardiac injury in septic mice. Neutralization of IL-16 may be a beneficial strategy for the prevention of cardiac injury and dysfunction in sepsis patients.

show abstract

Interleukin-12p35 deficiency enhances mitochondrial dysfunction and aggravates cardiac remodeling in aging mice

Cited by 18 publications

References 30 publications

Interleukin-22 deficiency alleviates doxorubicin-induced oxidative stress and cardiac injury via the p38 MAPK/macrophage/Fizz3 axis in mice

Interleukin-22 deficiency alleviates doxorubicin-induced oxidative stress and cardiac injury via the p38 MAPK/macrophage/Fizz3 axis in mice

Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges

Anti‐Interleukin‐16 Neutralizing Antibody Treatment Alleviates Sepsis‐Induced Cardiac Injury and Dysfunction via the Nuclear Factor Erythroid‐2 Related Factor 2 Pathway in Mice

Contact Info

Product

Resources

About