Abstract
Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and both innate and adaptive immunity contribute to the pathogenesis. Kidney resident cells promote inflammation after IRI by increasing endothelial cell adhesion molecule expression and vascular permeability. Kidney epithelial cells bind complement and express tolllike receptors and resident and infiltrating cells produce cytokines/chemokines. Early activation of kidney dendritic cells (DCs) initiates a cascade of events leading to accumulation of interferon-γ-producing neutrophils, infiltrating macrophages, CD4+ T cells, B cells and invariant natural killer T (NKT) cells. Recent studies from our laboratory now implicate the IL23/IL17 pathway in kidney IRI. Following the initial early phase of inflammation, the late phase involves infiltration of anti-inflammatory cells including regulatory T cells, alternatively activated macrophages and stem cells leading to attenuation of inflammation and initiation of repair. Based upon these immune mechanisms of injury, recent studies hold promise for novel drug therapies. These pharmacological agents have been shown to reduce inflammation or cytotoxicity in rodent models of AKI and some show early promise in clinical trials. This review summarizes recent advances to further our understanding of the immune mechanisms of AKI and potential pharmacological therapies.
Keywords: Acute renal failure, ischemia-reperfusion injury, cisplatin, inflammation
Current Drug Targets
Title: Immune Mechanisms and Novel Pharmacological Therapies of Acute Kidney Injury
Volume: 10 Issue: 12
Author(s): Amandeep Bajwa, Gilbert R. Kinsey and Mark D. Okusa
Affiliation:
Keywords: Acute renal failure, ischemia-reperfusion injury, cisplatin, inflammation
Abstract: Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and both innate and adaptive immunity contribute to the pathogenesis. Kidney resident cells promote inflammation after IRI by increasing endothelial cell adhesion molecule expression and vascular permeability. Kidney epithelial cells bind complement and express tolllike receptors and resident and infiltrating cells produce cytokines/chemokines. Early activation of kidney dendritic cells (DCs) initiates a cascade of events leading to accumulation of interferon-γ-producing neutrophils, infiltrating macrophages, CD4+ T cells, B cells and invariant natural killer T (NKT) cells. Recent studies from our laboratory now implicate the IL23/IL17 pathway in kidney IRI. Following the initial early phase of inflammation, the late phase involves infiltration of anti-inflammatory cells including regulatory T cells, alternatively activated macrophages and stem cells leading to attenuation of inflammation and initiation of repair. Based upon these immune mechanisms of injury, recent studies hold promise for novel drug therapies. These pharmacological agents have been shown to reduce inflammation or cytotoxicity in rodent models of AKI and some show early promise in clinical trials. This review summarizes recent advances to further our understanding of the immune mechanisms of AKI and potential pharmacological therapies.
Export Options
About this article
Cite this article as:
Bajwa Amandeep, Kinsey R. Gilbert and Okusa D. Mark, Immune Mechanisms and Novel Pharmacological Therapies of Acute Kidney Injury, Current Drug Targets 2009; 10 (12) . https://dx.doi.org/10.2174/138945009789753174
DOI https://dx.doi.org/10.2174/138945009789753174 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Aging is Neuroprotective During Global Ischemia but Leads to Increased Caspase-3 and Apoptotic Activity in Hippocampal Neurons
Current Neurovascular Research Importance of Aquaporins in the Physiopathology of Brain Edema
Current Pharmaceutical Design Uric Acid and Cu/Zn Superoxide Dismutase: Potential Strategies and Biomarkers in Functional Recovery of Post-Acute Ischemic Stroke Patients after Intensive Neurorehabilitation
Current Neurovascular Research Heart Disease Induced by AAS Abuse, Using Experimental Mice/Rats Models and the Role of Exercise-Induced Cardiotoxicity
Mini-Reviews in Medicinal Chemistry Potential of Bone Marrow Stromal Cells in Applications for Neuro-Degenerative, Neuro-Traumatic and Muscle Degenerative Diseases
Current Neuropharmacology Diabetes-induced Epigenetic Signature in Vascular Cells
Endocrine, Metabolic & Immune Disorders - Drug Targets Role of Citicoline in Promoting the Repair of Acute Peripheral Nerve Injury in Rat Models
Neuroscience and Biomedical Engineering (Discontinued) Ascorbic Acid in Postoperative Intensive Care Patients - Biochemical Aspects and Clinical Experience
Current Medicinal Chemistry Matrix Metalloproteinase Inhibitors as Prospective Agents for the Prevention and Treatment of Cardiovascular and Neoplastic Diseases
Current Topics in Medicinal Chemistry Histone Deacetylase Inhibitors In Inflammatory Disease
Current Topics in Medicinal Chemistry Enhanced Neuroprotection of Ischemic Stroke Based on Liposomal Drug Delivery System Loading a Novel Uncoupler of Ischemia-induced nNOSPSD- 95
Current Signal Transduction Therapy Current Status of Pharmacological Thrombolytic Therapy and Mechanical Thrombectomy for the Treatment of Acute Deep Venous Thrombosis
Cardiovascular & Hematological Agents in Medicinal Chemistry Targeting α7 Nicotinic Acetylcholine Receptor to Combat Inflammation in Cardio-Cerebral-Vascular Diseases
Current Drug Targets Nuezhenide Exerts Anti-Inflammatory Activity through the NF-κB Pathway
Current Molecular Pharmacology The Role of Stem Cell Factor and Granulocyte-Colony Stimulating Factor in Treatment of Stroke
Recent Patents on CNS Drug Discovery (Discontinued) Syntheses, Transformations and Pharmaceutical Applications of Kynurenic Acid Derivatives
Current Medicinal Chemistry Melatonin Leads to Axonal Regeneration, Reduction in Oxidative Stress, and Improved Functional Recovery Following Sciatic Nerve Injury
Current Neurovascular Research Functional Genomics of Cardioprotection by Ischemic Conditioning and the Influence of Comorbid Conditions: Implications in Target Identification
Current Drug Targets Towards More Efficient Glutathione Peroxidase Mimics: Substrate Recognition and Catalytic Group Assembly
Current Medicinal Chemistry Hydrogen Sulfide and Inflammatory Joint Diseases
Current Drug Targets