Treatment with<scp>IL‐19</scp>improves locomotor functional recovery after contusion trauma to the spinal cord

Guo, Ji-Ming; Wang, Hua-dong; Li, Li; Yuan, Yifang; Shi, Xiuxiu; Hou, Shuxun

doi:10.1111/bph.14193

Cited by 16 publications

(15 citation statements)

References 41 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, Lu et al had verified that fibroblast growth factor 21 improved functional recovery and axonal regeneration through regulating oxidative stress after PNI [59]. Reducing excessive oxidative stress improves the locomotor functional recovery after SCI [60]. One previous study has also demonstrated that metformin restores mitochondrial biogenesis by inhibiting of the PDK4/oxidative stress-mediated apoptosis pathway [61].…”

Section: Discussionmentioning

confidence: 99%

Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule

Wang

Zheng

Han

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Spinal cord injury (SCI) is a devastating disease that may lead to lifelong disability. Thus, seeking for valid drugs that are beneficial to promoting axonal regrowth and elongation after SCI has gained wide attention. Metformin, a glucose-lowering agent, has been demonstrated to play roles in various central nervous system (CNS) disorders. However, the potential protective effect of metformin on nerve regeneration after SCI is still unclear. In this study, we found that the administration of metformin improved functional recovery after SCI through reducing neuronal cell apoptosis and repairing neurites by stabilizing microtubules via PI3K/Akt signaling pathway. Inhibiting the PI3K/Akt pathway with LY294002 partly reversed the therapeutic effects of metformin on SCI in vitro and vivo. Furthermore, metformin treatment weakened the excessive activation of oxidative stress and improved the mitochondrial function by activating the nuclear factor erythroid-related factor 2 (Nrf2) transcription and binding to the antioxidant response element (ARE). Moreover, treatment with Nrf2 inhibitor ML385 partially abolished its antioxidant effect. We also found that the Nrf2 transcription was partially reduced by LY294002 in vitro. Taken together, these results revealed that the role of metformin in nerve regeneration after SCI was probably related to stabilization of microtubules and inhibition of the excessive activation of Akt-mediated Nrf2/ARE pathway-regulated oxidative stress and mitochondrial dysfunction. Overall, our present study suggests that metformin administration may provide a potential therapy for SCI.

show abstract

Section: Discussionmentioning

confidence: 99%

Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule

Wang

Zheng

Han

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Thus, the decreased plasma IL-17 and IL-23 level in survivors implicate a remarkable reduction of organ injury induced by ischemia, whereas the elevation of IL-17 in non-survivors suggests an aggravation of ischemic injury. It should be noted that several other interleukins such as IL-19 and IL-21 also contribute to myocardial injury during ischemia [57][58][59], so we may need more investigation on them in the future.…”

Section: Discussionmentioning

confidence: 99%

High plasma levels of pro-inflammatory factors interleukin-17 and interleukin-23 are associated with poor outcome of cardiac-arrest patients: a single center experience

Zhuang

Chen

Zhou

et al. 2020

BMC Cardiovasc Disord

View full text Add to dashboard Cite

Background: Systemic inflammation is an important feature of post-cardiac arrest syndrome (PCAS). This study was designed to determine whether the plasma concentrations of some circulating pro-inflammatory cytokines , IL-22, IL-23 and IL-33) are of value in predicting the outcome of patients after return of spontaneous circulation (ROSC) during the post-cardiac arrest period. Methods: This was a prospective observational clinical study. In total, 21 patients (survivors, n = 10; non-survivors, n = 11) who experienced cardiac arrest and successful ROSC with expected survival of at least 7 days were consecutively enrolled from January 2016 to December 2017. Of the 21 enrolled patients, ten survived were designated "survivors". The other eleven patients died between 2 days and 1 months post ROSC. Venous blood was drawn at three time-points: baseline (< 1 h post ROSC), 2 days post ROSC and 7 days post ROSC. Plasma IL-8, IL-22, IL-23 and IL-33 were determined using commercial enzyme-linked immunosorbent assays. Results: Plasma creatinine levels, but aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were elevated in non-survivors compared with survivors. Plasma levels of IL-17, IL-22, IL-23 and IL-33 of the 21 total patients did not change at 2 or 7 days post ROSC compared to baseline. In survivors, the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were lower than baseline. In non-survivors, plasma levels of IL-17 increased compared with baseline. Receiver operating characteristic curve analysis showed that the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were able to predict the mortality of PCAS patients, and positively correlated with Acute Physiology and Chronic Health Evaluation (APACHE)-II score and time to ROSC.Conclusion: These results provide the first evidence that the elevated plasma IL-17 and IL-23 levels are associated with poor outcome in PCAS patients. The role of IL-17/IL-23 axis post ROSC is worth paying attention to in PCAS patients.Trial registration: Clinicaltrial.gov NCT02297776, 2014-11-21.

show abstract

“…Then, we examined whether exogenous IL-19 abolishes the effect of IL-19 deficiency in EAE. According to the previous studies showing that the daily administration of IL-19 protein (10 ng/g of body weight) can offset IL-19 deficiency ( 29 , 30 ), we firstly treated WT and IL-19 −/− EAE mice with recombinant mouse IL-19 protein (10 ng/g of body weight) or PBS by intraperitoneal injection every day. However, even daily injection with PBS caused mice severe stress which markedly suppressed EAE development ( 33 ).…”

Section: Resultsmentioning

confidence: 99%

“…The mice were intraperitoneally injected with 200 ng pertussis toxin on days 0 and 2 post-immunization. To investigate the effect of IL-19, EAE mice were treated with mouse recombinant IL-19 protein (20 ng/g of body weight) by intraperitoneal injection every other day starting on day 2 post-immunization, according to a modification of a previously reported method ( 29 , 30 ). The mice were assessed daily for clinical signs of EAE, according to the following grading system: 0, normal; 1, limp tail or mild hind limb weakness; 2, moderate hind limb weakness or mild ataxia; 3, moderate to severe hind limb weakness; 4, severe hind limb weakness, mild forelimb weakness or moderate ataxia; 5, paraplegia with moderate forelimb weakness; and 6, paraplegia with severe forelimb weakness, severe ataxia, or moribundity.…”

Section: Methodsmentioning

confidence: 99%

Interleukin-19 Abrogates Experimental Autoimmune Encephalomyelitis by Attenuating Antigen-Presenting Cell Activation

et al. 2021

View full text Add to dashboard Cite

Interleukin-19 (IL-19) acts as a negative-feedback regulator to limit proinflammatory response of macrophages and microglia in autocrine/paracrine manners in various inflammatory diseases. Multiple sclerosis (MS) is a major neuroinflammatory disease in the central nervous system (CNS), but it remains uncertain how IL-19 contributes to MS pathogenesis. Here, we demonstrate that IL-19 deficiency aggravates experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by promoting IL-17-producing helper T cell (Th17 cell) infiltration into the CNS. In addition, IL-19-deficient splenic macrophages expressed elevated levels of major histocompatibility complex (MHC) class II, co-stimulatory molecules, and Th17 cell differentiation-associated cytokines such as IL-1β, IL-6, IL-23, TGF-β1, and TNF-α. These observations indicated that IL-19 plays a critical role in suppression of MS pathogenesis by inhibiting macrophage antigen presentation, Th17 cell expansion, and subsequent inflammatory responses. Furthermore, treatment with IL-19 significantly abrogated EAE. Our data suggest that IL-19 could provide significant therapeutic benefits in patients with MS.

show abstract

Treatment withIL‐19improves locomotor functional recovery after contusion trauma to the spinal cord

Abstract: IL-19 treatment reduced secondary injuries and improved locomotor functional recovery after contusion SCI, through diverse mechanisms including immune cell polarization, angiogenesis and anti-oxidative responses.

Cited by 16 publications

References 41 publications

Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule

Metformin Promotes Axon Regeneration after Spinal Cord Injury through Inhibiting Oxidative Stress and Stabilizing Microtubule

High plasma levels of pro-inflammatory factors interleukin-17 and interleukin-23 are associated with poor outcome of cardiac-arrest patients: a single center experience

Interleukin-19 Abrogates Experimental Autoimmune Encephalomyelitis by Attenuating Antigen-Presenting Cell Activation

Contact Info

Product

Resources

About