Beneficial impact of cathelicidin on hypersensitivity pneumonitis treatment-In vivo studies

PLoS One. 2021 May 17;16(5):e0251237. doi: 10.1371/journal.pone.0251237. eCollection 2021.

Abstract

Cathelicidin (CRAMP) is a defence peptide with a wide range of biological responses including antimicrobial, immunomodulatory and wound healing. Due to its original properties the usefulness of CRAMP in the treatment of pulmonary fibrosis was assessed in a murine model of hypersensitivity pneumonitis (HP). The studies were conducted on mouse strain C57BL/6J exposed to a saline extract of Pantoea agglomerans cells (HP inducer). Cathelicidin was administered in the form of an aerosol during and after HP development. Changes in the composition of immune cell populations (NK cells, macrophages, lymphocytes: Tc, Th, Treg, B), were monitored in lung tissue by flow cytometry. Extracellular matrix deposition (collagens, hydroxyproline), the concentration of cytokines involved in inflammatory and the fibrosis process (IFNγ, TNFα, TGFβ1, IL1β, IL4, IL5, IL10, IL12α, IL13) were examined in lung homogenates by the ELISA method. Alterations in lung tissue morphology were examined in mouse lung sections stained with haematoxylin and eosin as well as Masson trichrome dyes. The performed studies revealed that cathelicidin did not cause any negative changes in lung morphology/structure, immune cell composition or cytokines production. At the same time, CRAMP attenuated the immune reaction induced by mice chronic exposure to P. agglomerans and inhibited hydroxyproline and collagen deposition in the lung tissue of mice treated with bacteria extract. The beneficial effect of CRAMP on HP treatment was associated with restoring the balance in quantity of immune cells, cytokines production and synthesis of extracellular matrix components. The presented study suggests the usefulness of cathelicidin in preventing lung fibrosis; however, cathelicidin was not able to reverse pathological changes completely.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols / pharmacology
  • Alveolitis, Extrinsic Allergic / drug therapy*
  • Alveolitis, Extrinsic Allergic / metabolism
  • Animals
  • Cathelicidins / pharmacology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Lung / drug effects
  • Lung / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Pantoea / metabolism
  • Pulmonary Fibrosis / drug therapy
  • Pulmonary Fibrosis / metabolism

Substances

  • Aerosols
  • Cathelicidins
  • Cytokines

Grants and funding

The study was supported by Grant No. 2015/19/D/NZ7/02952 "The evaluation of cathelicidin preventive and therapeutic properties against pulmonary fibrosis. In vivo and molecular studies in the mice model of hypersensitivity pneumonitis” from the National Science Centre, Poland. Marta K. Lemieszek, Katarzyna Sawa-Wejksza, Jacek Zwoliński and Janusz Milanowski received remuneration from the grant implementation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.