JMV5656, a short synthetic derivative of TLQP-21, alleviates acid-induced lung injury and fibrosis in mice. (June 2020)

• Record Type: Journal Article
• Authors: Zambelli, Vanessa; Rizzi, Laura; Delvecchio, Paolo; Bresciani, Elena; Molteni, Laura; Meanti, Ramona; Pascal, Verdiè; Fehrentz, Jean-Alain; Omeljaniuk, Robert J.; Bellani, Giacomo; Torsello, Antonio
• Is Part Of: Pulmonary pharmacology & therapeutics. Volume 62(2020)
• Publication Date: 2020-06
• Subjects: JMV5656 -- TLQP-21 -- ARDS -- Inflammation -- Lung fibrosis; Respiratory organs -- Diseases -- Chemotherapy -- Periodicals; 615.7205
• DOI: 10.1016/j.pupt.2020.101916
• Languages: English
• ISSNs: 1094-5539

Abstract

Abstract: TLQP-21, a peptide encoded by the prohormone VGF, is expressed in neuroendocrine cells and can modulate inflammatory processes. Since TLQP-21 can bind the complement 3a receptor 1 on macrophages, interest has risen in this peptide as a potential drug for the treatment of Acute Respiratory Distress Syndrome (ARDS), whose hospital mortality can reach 35–46%. Since no effective pharmacologic therapies are available, our aim was to exploit the potential of a short analog of TLQP-21(JMV5656) in order to modulate the inflammatory process in ARDS and the progression to pulmonary fibrosis in an experimental model of unilateral acid aspiration in mice. Mice were divided in 2 treatment groups. In the acute protocol, mice received intra-peritoneal injection of either vehicle or 0.6 mg/kg JMV5656 on experimental days 1 and 2, and ARDS was induced on day 3 under deep anesthesia by instillation of HCl (1.5 ml/kg of 0.1 M HCl in 0.9% NaCl) into the right lung; all measurements were performed 24 h later. In the subacute protocol, mice were treated as previously, but treatment with vehicle or JMV5656 was repeated also on day 4 and measurements were made 2 weeks later. Twenty-four hours after acid instillation, the total number of immune cell in the BAL rose sharply due primarily to an increase in the PMN population which increased from 1% up to 58% of total cell numbers. JMV5656 significantly reduced PMN recruitment into the alveolar space, but had no effects on cytokine levels in BAL. Two weeks after acid injury, static compliance of the right lung was significantly higher in the JMV5656-treated group compared to vehicle-treated group. Treatment with JMV5656 also blunted the acid-induced collagen deposition in the right lung. These results suggest that JMV5656 can ameliorate mechanical compliance, and reduce collagen deposition in acid-injured lungs in mice. This effect was likely due to the ability of JMV5656 to inhibit PMN recruitment in the injured lung.