Biodistribution and Efficacy of Targeted Pulmonary Delivery of a Protein Kinase C-δ Inhibitory Peptide: Impact on Indirect Lung Injury
| Autor: | Matthew Kauffman, Paul A. Kennedy, Jichuan Wu, Linda C. Knight, Sandy T. Baker, Marla R. Wolfson, Laurie E. Kilpatrick, Mark J. Mondrinos |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Pathology medicine.medical_specialty Biodistribution Anti-Inflammatory Agents Inflammation Pharmacology Lung injury Pulmonary function testing Rats Sprague-Dawley Sepsis Intensive care medicine Animals Tissue Distribution Lung Protein Kinase Inhibitors Dose-Response Relationship Drug Pulmonary Gas Exchange business.industry Kinase Technetium Biological Transport Lung Injury Pneumonia Inflammation Immunopharmacology and Asthma medicine.disease Peptide Fragments Rats Protein Kinase C-delta medicine.anatomical_structure Gene Products tat Disease Progression Molecular Medicine medicine.symptom business |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 355:86-98 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | Sepsis and sepsis-induced lung injury remain a leading cause of death in intensive care units. We identified protein kinase C-δ (PKCδ) as a critical regulator of the acute inflammatory response and demonstrated that PKCδ inhibition was lung-protective in a rodent sepsis model, suggesting that targeting PKCδ is a potential strategy for preserving pulmonary function in the setting of indirect lung injury. In this study, whole-body organ biodistribution and pulmonary cellular distribution of a transactivator of transcription (TAT)–conjugated PKCδ inhibitory peptide (PKCδ-TAT) was determined following intratracheal (IT) delivery in control and septic [cecal ligation and puncture (CLP)] rats to ascertain the impact of disease pathology on biodistribution and efficacy. There was negligible lung uptake of radiolabeled peptide upon intravenous delivery [65% ID with minimal uptake in liver or kidney ( |
| Databáze: | OpenAIRE |
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