Egr-1 functions as a master switch regulator of remote ischemic preconditioning-induced cardioprotection

Billah, Muntasir; Ridiandries, Anisyah; Bs, Rayner; Allahwala, U.; Dona, Anthony C.; Lm, Khachigian; Bhindi, Ravinay

doi:10.1007/s00395-019-0763-9

Cited by 29 publications

(29 citation statements)

References 120 publications

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“…RHPC and H/R were performed as previously described [32,114]. 'Hypoxic media' was directly bubbled with nitrogen for 15 min to achieve less than 2% O 2 followed by tightly closing the lid.…”

Section: In Vitro H/r Injury Modelmentioning

confidence: 99%

“…As we used specific weighted and aged rats, and cut the heart in equal size slices, it is expected that the variance in terms of the weight of slices across the groups was minimal. In addition, the percentage of infarct size/AAR has been widely used to measure infarct size in vivo [32,114,128,129]. Hind limb tissue at the RIPC site was collected and immediately frozen in dry ice.…”

Section: Measurement Of Myocardial Infarct Size and Tissue Collectionmentioning

confidence: 99%

“…Total proteins have been widely used to confirm even loading [134,135]. We have previously published using the total expression of protein to demonstrate equal loading for phosphorylated proteins without any issue [32,114].…”

Section: Western Blottingmentioning

confidence: 99%

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Remote Ischemic Preconditioning Induces Cardioprotective Autophagy and Signals through the IL-6-Dependent JAK-STAT Pathway

Billah

Ridiandries

Allahwala

et al. 2020

IJMS

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Autophagy is a cellular process by which mammalian cells degrade and assist in recycling damaged organelles and proteins. This study aimed to ascertain the role of autophagy in remote ischemic preconditioning (RIPC)-induced cardioprotection. Sprague Dawley rats were subjected to RIPC at the hindlimb followed by a 30-min transient blockade of the left coronary artery to simulate ischemia reperfusion (I/R) injury. Hindlimb muscle and the heart were excised 24 h post reperfusion. RIPC prior to I/R upregulated autophagy in the rat heart at 24 h post reperfusion. In vitro, autophagy inhibition or stimulation prior to RIPC, respectively, either ameliorated or stimulated the cardioprotective effect, measured as improved cell viability to mimic the preconditioning effect. Recombinant interleukin-6 (IL-6) treatment prior to I/R increased in vitro autophagy in a dose-dependent manner, activating the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway without affecting the other kinase pathways, such as p38 mitogen-activated protein kinases (MAPK), and glycogen synthase kinase 3 Beta (GSK-3β) pathways. Prior to I/R, in vitro inhibition of the JAK-STAT pathway reduced autophagy upregulation despite recombinant IL-6 pre-treatment. Autophagy is an essential component of RIPC-induced cardioprotection that may upregulate autophagy through an IL-6/JAK-STAT-dependent mechanism, thus identifying a potentially new therapeutic option for the treatment of ischemic heart disease.

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Section: In Vitro H/r Injury Modelmentioning

confidence: 99%

Section: Measurement Of Myocardial Infarct Size and Tissue Collectionmentioning

confidence: 99%

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Remote Ischemic Preconditioning Induces Cardioprotective Autophagy and Signals through the IL-6-Dependent JAK-STAT Pathway

Billah

Ridiandries

Allahwala

et al. 2020

IJMS

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“…This suggests that resident splenic (and possibly circulating) T cells and B cells were the sources of the SnPP-triggered the five-to sevenfold plasma IL-10 increases. Although IL-6 has long been considered to be a pro-inflammatory cytokine, it also exerts potent anti-inflammatory effects (Billah et al, 2019(Billah et al, , 2020Filho et al, 2015;Kimizuka et al, 2004;McGinnis et al, 2015;Nechemia-Arbely et al, 2008). As examples, IL-6 can suppress production of pro-inflammatory cytokines and their receptors.…”

Section: Discussionmentioning

confidence: 99%

“…It also stimulates glucocorticoid (Bethin, Vogt, & Muglia, 2000) and IL-10 production (Andres-Hernando et al, 2017;Soranno et al, 2016). Exogenous IL-6 administration has been reported to mitigate inflammation during ischemic-reperfusion injury (Billah et al, 2019;Kimizuka et al, 2004). Furthermore, endogenous IL-6 has been implicated as a mediator of remote-as well as of direct-ischemic preconditioning (Billah et al, 2019;Kimizuka et al, 2004;Nechemia-Arbely et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

The NRF2 stimulating agent, tin protoporphyrin, activates protective cytokine pathways in healthy human subjects and in patients with chronic kidney disease

Zager

Johnson

2020

Physiol. Rep.

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Background Tin protoporphyrin (SnPP), a heme oxygenase 1 (HO‐1) inhibitor, triggers adaptive tissue responses that confer potent protection against acute renal‐ and extra‐renal tissue injuries. This effect is mediated, in part, via SnPP‐induced activation of the cytoprotective Nrf2 pathway. However, it remains unclear as to whether SnPP can also upregulate humoral cytokine defenses, either in healthy human subjects or in patients with CKD. If so, then systemically derived cytokines could contribute SnPP‐induced tissue protection. Methods SnPP (90 mg IV) was administered over 2 hr to six healthy human volunteers (HVs) and 12 subjects with stage 3–4 CKD. Plasma samples were obtained from baseline upto 72 hr post injection. Two representative anti‐inflammatory cytokines (IL‐10, TGFβ1), and a pro‐inflammatory cytokine (TNF‐α), were assayed. Because IL‐6 has been shown to induce tissue preconditioning, its plasma concentrations were also assessed. In complementary mouse experiments, SnPP effects on renal, splenic, and hepatic IL‐10, IL‐6, TGFβ1, and TNF‐α production (as gauged by their mRNAs) were tested. Tissue HO‐1 mRNA served as an Nrf2 activation marker. Results SnPP induced marked (~5–7x) increases in plasma IL‐10 and IL‐6 concentrations within 24–48 hr, and to equal degrees in HVs and CKD patients. SnPP modestly raised plasma TGFβ1 without impacting plasma TNF‐α levels. In mouse experiments, SnPP did not affect IL‐6, IL‐10, TNF‐α, or TGFβ1 mRNAs in kidney despite marked renal Nrf2 activation. Conversely, SnPP increased splenic IL‐10 and hepatic IL‐6/TGFβ1 mRNA levels, suggesting these organs as sites of extra‐renal cytokine generation. Conclusions SnPP can trigger cytoprotective cytokine production, most likely in extra‐renal tissues. With ready glomerular cytokine filtration, extra‐renal/renal “organ cross talk” can result. Thus, humoral factors seemingly can contribute to SnPP’s cytoprotective effects.

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Does remote ischaemic conditioning reduce inflammation? A focus on innate immunity and cytokine response

Pearce¹,

Davidson²,

Yellon³

2021

Basic Res Cardiol

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The benefits of remote ischaemic conditioning (RIC) have been difficult to translate to humans, when considering traditional outcome measures, such as mortality and heart failure. This paper reviews the recent literature of the anti-inflammatory effects of RIC, with a particular focus on the innate immune response and cytokine inhibition. Given the current COVID-19 pandemic, the inflammatory hypothesis of cardiac protection is an attractive target on which to re-purpose such novel therapies. A PubMed/MEDLINE™ search was performed on July 13th 2020, for the key terms RIC, cytokines, the innate immune system and inflammation. Data suggest that RIC attenuates inflammation in animals by immune conditioning, cytokine inhibition, cell survival and the release of anti-inflammatory exosomes. It is proposed that RIC inhibits cytokine release via a reduction in nuclear factor kappa beta (NF-κB)-mediated NLRP3 inflammasome production. In vivo, RIC attenuates pro-inflammatory cytokine release in myocardial/cerebral infarction and LPS models of endotoxaemia. In the latter group, cytokine inhibition is associated with a profound survival benefit. Further clinical trials should establish whether the benefits of RIC in inflammation can be observed in humans. Moreover, we must consider whether uncomplicated MI and elective surgery are the most suitable clinical conditions in which to test this hypothesis.

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Egr-1 functions as a master switch regulator of remote ischemic preconditioning-induced cardioprotection

Cited by 29 publications

References 120 publications

Remote Ischemic Preconditioning Induces Cardioprotective Autophagy and Signals through the IL-6-Dependent JAK-STAT Pathway

Remote Ischemic Preconditioning Induces Cardioprotective Autophagy and Signals through the IL-6-Dependent JAK-STAT Pathway

The NRF2 stimulating agent, tin protoporphyrin, activates protective cytokine pathways in healthy human subjects and in patients with chronic kidney disease

Does remote ischaemic conditioning reduce inflammation? A focus on innate immunity and cytokine response

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