Novel Immunomodulatory Cytokine Regulates Inflammation, Diabetes, and Obesity to Protect From Diabetic Nephropathy

Sabapathy, Vikram; Stremska, Marta E.; Saleh, Mohammad; Corey, Rebecca; Sharma, Poonam; Sharma, Rahul

doi:10.3389/fphar.2019.00572

Cited by 36 publications

(25 citation statements)

References 60 publications

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“…Further, numerous pharmacological treatments aiming to reduce inflammation in metabolic diseases have positive effects on glucose tolerance in mice and human. These include the novel hybrid cytokine interleukin (IL) 233, which is produced in a genetically modified Escherichia coli by fusing murine IL-2 and murine IL-33 (14). Other treatment strategies include IL-1 receptor blockage (15), IL-1β antagonism (16), inhibition of the intracellular pro-inflammatory NF-κB pathway (17), and TNF antagonism (18) (Figure 2).…”

Section: Inflammation In Obesity and Type 2 Diabetesmentioning

confidence: 99%

Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes

et al. 2020

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The gut microbiota has been linked to the development of obesity and type 2 diabetes (T2D). The underlying mechanisms as to how intestinal microbiota may contribute to T2D are only partly understood. It becomes progressively clear that T2D is characterized by a chronic state of low-grade inflammation, which has been linked to the development of insulin resistance. Here, we review the current evidence that intestinal microbiota, and the metabolites they produce, could drive the development of insulin resistance in obesity and T2D, possibly by initiating an inflammatory response. First, we will summarize major findings about immunological and gut microbial changes in these metabolic diseases. Next, we will give a detailed view on how gut microbial changes have been implicated in low-grade inflammation. Lastly, we will critically discuss clinical studies that focus on the interaction between gut microbiota and the immune system in metabolic disease. Overall, there is strong evidence that the tripartite interaction between gut microbiota, host immune system and metabolism is a critical partaker in the pathophysiology of obesity and T2D.

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Section: Inflammation In Obesity and Type 2 Diabetesmentioning

confidence: 99%

Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes

et al. 2020

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“…- A role in the recruitment and acquisition of T regulatory lymphocytes' innate competences IL-33 is implicated in the recruitment of T regulatory (Treg) lymphocytes during renal IR injury (46), and is associated with improved renal IR injury tolerance. Furthermore, the eutrophic functions of Treg lymphocytes present in visceral adipose tissue are dependent on the production of IL-33 by the stromal cells in adipose tissue (47, 48).…”

Section: The Expanding Family Of Interleukin (Il)-1 Cytokines and Thementioning

confidence: 99%

“…A recent study highlighted the beneficial effects of IL-233 in prevention of diabetic nephropathy in an Ob type 2 diabetes (DT2) mouse model. In this mouse model of predisposition to obesity and DT2 on account of an Ob mutation of leptin rendering the latter non-functional, IL233 treatment during or after the appearance of DT2 provides protection from diabetic nephropathy (46).…”

Section: Therapeutic Perspectivesmentioning

confidence: 99%

Interleukin-1 Family Cytokines: Keystones in Liver Inflammatory Diseases

et al. 2019

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The pyrogenic property being the first activity described, members of the interleukin-1 superfamily (IL-1α, IL-1β, IL-18, and the newest members: IL-33, IL-36, IL-37, and IL-38) are now known to be involved in several inflammatory diseases such as obesity, atherosclerosis, cancer, viral and parasite infections, and auto-inflammatory syndromes as well as liver diseases. Inflammation processes are keystones of chronic liver diseases, of which the etiology may be viral or toxic, as in alcoholic or non-alcoholic liver diseases. Inflammation is also at stake in acute liver failure involving massive necrosis, and in ischemia-reperfusion injury in the setting of liver transplantation. The role of the IL-1 superfamily of cytokines and receptors in liver diseases can be either protective or pro-inflammatory, depending on timing and the environment. Our review provides an overview of current understanding of the IL-1 family members in liver inflammation, highlighting recent key investigations, and therapeutic perspectives. We have tried to apply the concept of trained immunity to liver diseases, based on the role of the members of the IL-1 superfamily, first of all IL-1β but also IL-18 and IL-33, in modulating innate lymphoid immunity carried by natural killer cells, innate lymphoid cells or innate T-αβ lymphocytes.

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“…It remains to be evaluated whether this may be either a direct effect of these cells or through inducing an anti-inflammatory milieu, which may be conducive for progenitor cells to promote regenerative responses. Treatment with IL233 after the onset of lupus nephritis and diabetic nephropathy in animal models also induced persistent remission, suggestive of a reparative role of IL-33 alarmin in chronic renal injury (170,196,197). Current studies in our group are addressing the role of the IL-33/ST2 and IL233 in the repair of renal injury in both an immune-dependent and independent manner.…”

Section: Implications Of Alarmins In Repair Post-akimentioning

confidence: 97%

The Yin and Yang of Alarmins in Regulation of Acute Kidney Injury

et al. 2020

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Acute kidney injury (AKI) is a major clinical burden affecting 20 to 50% of hospitalized and intensive care patients. Irrespective of the initiating factors, the immune system plays a major role in amplifying the disease pathogenesis with certain immune cells contributing to renal damage, whereas others offer protection and facilitate recovery. Alarmins are small molecules and proteins that include granulysins, high-mobility group box 1 protein, interleukin (IL)-1α, IL-16, IL-33, heat shock proteins, the Ca ++ binding S100 proteins, adenosine triphosphate, and uric acid. Alarmins are mostly intracellular molecules, and their release to the extracellular milieu signals cellular stress or damage, generally leading to the recruitment of the cells of the immune system. Early studies indicated a proinflammatory role for the alarmins by contributing to immune-system dysregulation and worsening of AKI. However, recent developments demonstrate anti-inflammatory mechanisms of certain alarmins or alarmin-sensing receptors, which may participate in the prevention, resolution, and repair of AKI. This dual function of alarmins is intriguing and has confounded the role of alarmins in AKI. In this study, we review the contribution of various alarmins to the pathogenesis of AKI in experimental and clinical studies. We also analyze the approaches for the therapeutic utilization of alarmins for AKI.

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Novel Immunomodulatory Cytokine Regulates Inflammation, Diabetes, and Obesity to Protect From Diabetic Nephropathy

Cited by 36 publications

References 60 publications

Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes

Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes

Interleukin-1 Family Cytokines: Keystones in Liver Inflammatory Diseases

The Yin and Yang of Alarmins in Regulation of Acute Kidney Injury

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