HO-1 and NLRP3-associated lung dysfunction and systemic inflammation in a noninfectious COVID-19 spike protein murine model.

Authors

Sophia Kwon, Joanna Zhou, Jamie Antelo Rivero, Hailey Bernier, Arul Veerappan, Mengling Liu, Gabriele Grunig, George Crowley, Anna Nolan

Published in

Scientific reports. Volume 16. Pages 36338. Epub Aug 01, 2026.

Abstract

The COVID-19 (C19) pandemic caused significant mortality often due to lung injury and systemic inflammation, but there is significant heterogeneity in severity, and the pathobiology is not well understood. We examined C19-induced pulmonary and inflammatory sequelae using a murine noninfectious model to further define the model's utility and to also understand the role of mediators such as heme oxgenase-1 (HO-1). K18-hACE2 male mice oropharyngeally aspirated C19-spike protein(SP) or equal volume control. After 72 h, pulmonary mechanics, bronchoalveolar lavage (BAL), plasma, snap-frozen right lung, and fixed/stained left lung for histologic injury assessment (Qupath) was collected. Cytokine elaboration in BAL and plasma was quantified (Luminex), and lung homogenates were probed for HO-1 and NLRP3 (Western). Statistical (SPSS and R) and pathways comparisons (Ingenuity Pathway Analysis) were made between control and C19-SP. C19-SP exposure significantly reduced inspiratory capacity and static lung compliance; tissue elastance and airway bronchoconstriction were increased. C19-SP exposure caused significant inflammation and thickened alveolar septae on histology. C19-SP exposure also led to inflammatory response in BAL and plasma with simultaneous activation of Type 1 and Type 2 pathways. NLRP3 and HO-1 protein expression is significantly increased after C19-SP. A noninfectious C19-SP murine model showed worsened lung parameters and increased inflammation. Increased expression of HO-1 and NLRP3 were associated with the inflammatory process after exposure to C19, consistent with findings in human cohorts. Further studies may focus on targeted knock in/knock down experiments and dose/time-course studies that probe the mechanistic relationship of HO-1 and NLRP3 in C19-related disease.
The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-58934-9.

PMID:
43019195
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.