Page 18 - M. Immunology

[M. Immunology-12]

Nuclear trafficking inhibition of SRTFs protects lung in

pneumonitis animals by suppressing cytokine storm

Gyunam Kim¹, Danbi Lee¹, Jieun Kim¹, Hakyoung Park¹, Jeonghun Kwak¹, Jaehwa Lee¹, Seungwoo Lee¹,
Jaewook Lee¹, Youngsil Choi¹, Daewoong Jo¹˙*

¹R&D Institute, Cellivery Therapeutics, Inc., Seoul 03929, South Korea

Acute respiratory distress syndrome (ARDS) is fatal disease caused by severe inflammation in lung after infection.

Excessive secretion of pro-inflammatory cytokine recruits immune cells and it results disruption of lung bronchi and
alveoli. To prevent the unregulated cytokine secretion, called cytokine storm, improved cell-permeable nuclear

import inhibitor (iCP-NI) has been developed by fusing hydrophobic cell-penetrating peptide (CPP) with nuclear
localization signal (NLS) and demonstrated its improved therapeutic applicability. iCP-NI suppressed expression of

inflammatory cytokines by inhibits translocation of SRTFs from cytoplasm to nucleus. iCP-NI reduced cytokines
(TNF-α: -55%, IL-6: -49%, MCP-1: -70%) in bronchoalveolar lavage fluids (BALFs) of lipopolysaccharide (LPS)-induced

bacterial pneumonitis animals and protect lung tissue. In viral pneumonitis, iCP-NI reduced immune cell recruitment
into the lung tissue (-107%) and decreased cytokines in BALFs (TNF-α: -79%, IL-6: -91%, MCP-1: -89%). These results

suggest that iCP-NI has potential as a novel medicine to treat the bacterial and viral pneumonitis caused by various
infections which accompany severe respiratory disorder and death.