Lymphocytes and ischemia-reperfusion injury

Linfert, Douglas R.; Chowdhry, Tayseer; Rabb, Hamid

doi:10.1016/j.trre.2008.08.003

Cited by 201 publications

(158 citation statements)

References 98 publications

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“…More recent data, however, suggest that T cells also participate in early inflammatory responses in AKI. 3 The recruitment of immune effector cells is facilitated by the upregulation of adhesion molecules on various cell types within the kidney. 4 Subsequently, the balance between proand anti-inflammatory mediators significantly affects the extent of tissue injury and repair after an acute event.…”

Section: Basic Concepts Of Inflammationmentioning

confidence: 99%

Inflammation in AKI

Rabb

Griffin

McKay

et al. 2016

Journal of the American Society of Nephrology

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469

343

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Inflammation is a complex biologic response that is essential for eliminating microbial pathogens and repairing tissue after injury. AKI associates with intrarenal and systemic inflammation; thus, improved understanding of the cellular and molecular mechanisms underlying the inflammatory response has high potential for identifying effective therapies to prevent or ameliorate AKI. In the past decade, much knowledge has been generated about the fundamental mechanisms of inflammation. Experimental work in small animal models has revealed many details of the inflammatory response that occurs within the kidney after typical causes of AKI, including insights into the molecular signals released by dying cells, the role of pattern recognition receptors, the diverse subtypes of resident and recruited immune cells, and the phased transition from destructive to reparative inflammation. Although this expansion of the basic knowledge base has increased the number of mechanistically relevant targets of intervention, progress in developing therapies that improve AKI outcomes by modulation of inflammation remains slow. In this article, we summarize the most important recent developments in understanding the inflammatory mechanisms of AKI, highlight key limitations of the commonly used animal models and clinical trial designs that may prevent successful clinical application, and suggest priority approaches for research toward clinical translation in this area.

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Section: Basic Concepts Of Inflammationmentioning

confidence: 99%

Inflammation in AKI

Rabb

Griffin

McKay

et al. 2016

Journal of the American Society of Nephrology

Self Cite

469

343

View full text Add to dashboard Cite

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“…It is believed that both the innate and adaptive immune systems have an important role in I/R injury (4)(5)(6). Previous studies focused on the role of innate immune response such as reactive oxygen species, cytokines and chemokines, the complement system, and neutrophils (4,7).…”

mentioning

confidence: 99%

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

Liu

Wen

Zhan

et al. 2015

The Journal of Immunology

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Intestinal ischemia/reperfusion (I/R) injury, in which macrophages play a key role, can cause high morbidity and mortality. The switch from classically (M1) to alternatively (M2) activated macrophages, which is dependent on the activation of STAT6 signaling, has been shown to protect organs from I/R injuries. In the current study, the effects of recombinant Trichinella spiralis cathepsin B–like protein (rTsCPB) on intestinal I/R injury and the potential mechanism related to macrophage phenotypes switch were investigated. In a mouse I/R model undergoing 60-min intestinal ischemia followed by 2-h or 7-d reperfusion, we demonstrated that intestinal I/R caused significant intestinal injury and induced a switch from M2 to M1 macrophages, evidenced by a decrease in levels of M2 markers (arginase-1 and found in inflammatory zone protein), an increase in levels of M1 markers (inducible NO synthase and CCR7), and a decrease in the ratio of M2/M1 macrophages. RTsCPB reversed intestinal I/R-induced M2–M1 transition and promoted M1-M2 phenotype switch evidenced by a significant decrease in M1 markers, an increase in M2 markers, and the ratio of M2/M1 macrophages. Meanwhile, rTsCPB significantly ameliorated intestinal injury and improved intestinal function and survival rate of animals, accompanied by a decrease in neutrophil infiltration and an increase in cell proliferation in the intestine. However, a selective STAT6 inhibitor, AS1517499, reversed the protective effects of rTsCPB by inhibiting M1 to M2 transition. These findings suggest that intestinal I/R injury causes a switch from M2 to M1 macrophages and that rTsCPB ameliorates intestinal injury by promoting STAT6-dependent M1 to M2 transition.

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“…21 Now we confirm that in this model, in which pre-transplant DSA were not present in WA rats, there was a massive formation of DSA probably due to early peri-transplant B-cell activation. [25][26][27] In this highly stringent model, intra-graft CD40 silencing was unable per se to reduce circulating DSA, as expected from local treatment. However, when combined with a sub-therapeutic dose of rapamycin, an additive systemic reduction was found.…”

Section: Discussionmentioning

confidence: 78%

In vivo therapeutic efficacy of intra-renal CD40 silencing in a model of humoral acute rejection

et al. 2011

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The humoral branch of the immune response has an important role in acute and chronic allograft dysfunction. The CD40/CD40L costimulatory pathway is crucial in B-and T-alloresponse. Our group has developed a new small interfering RNA (siRNA) molecule against CD40 that effectively inhibits its expression. The aim of the present study was to prevent rejection in an acute vascular rejection model of kidney transplant by intra-graft gene silencing with anti-CD40 siRNA (siCD40), associated or not with sub-therapeutic rapamycin. Four groups were designed: unspecific siRNA as control; sub-therapeutic rapamycin; siCD40; and combination therapy. Long-surviving rats were found only in both siCD40-treated groups. The CD40 mRNA was overexpressed in control grafts but treatment with siCD40 decreased its expression. Recipient spleen CD40+ B-lymphocytes were reduced in both siCD40-treated groups. Moreover, CD40 silencing reduced donor-specific antibodies, graft complement deposition and immune-inflammatory mediators. The characteristic histological features of humoral rejection were not found in siCD40-treated grafts, which showed a more cellular histological pattern. Therefore, the intra-renal effective blockade of the CD40/CD40L signal reduces the graft inflammation as well as the incidence of humoral vascular acute rejection, finally changing the type of rejection from humoral to cellular. Gene Therapy (2011) 18, 945-952;

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Lymphocytes and ischemia-reperfusion injury

Cited by 201 publications

References 98 publications

Inflammation in AKI

Inflammation in AKI

Treatment with Recombinant Trichinella spiralis Cathepsin B–like Protein Ameliorates Intestinal Ischemia/Reperfusion Injury in Mice by Promoting a Switch from M1 to M2 Macrophages

In vivo therapeutic efficacy of intra-renal CD40 silencing in a model of humoral acute rejection

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