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Loss of Nucleobindin-2/Nesfatin-1 increases lipopolysaccharide-induced murine acute lung inflammation

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Abstract

NUCB2/nesfatin-1 is expressed in variety of tissues. Treatment with nesfatin-1 reduces inflammation in rat models of subarachnoid hemorrhage-induced oxidative brain damage and traumatic brain injury as well as myocardial injury. There is only one study showing anti-inflammatory actions of nesfatin-1 on acute lung inflammation. To more precisely determine the role of NUCB2/nesfatin-1 in acute lung inflammation, we conducted a study using NUCB2/nesfatin-1 knockout (NKO) mice as well as neutrophils isolated from the bone marrows of WT and NKO mice. Our findings suggest that the absence of NUCB2/nesfatin-1 significantly increases the accumulation of adherent neutrophils by approximately 3 times compared with WT within LPS-treated lungs. Integrating this with observations from both BALF and neutrophil cytokine expression, we propose that although neutrophils lacking NUCB2/nesfatin-1 individually secrete less pro-inflammatory cytokines compared with stimulated WT cells, the result of knocking out NUCB2/nesfatin-1 is net pro-inflammatory. No change was found in NUCB2/nesfatin-1 mRNA or protein expression comparing WT LPS and PBS-treated samples. Taken together, our results show that NUCB2/nesfatin-1 is constitutively expressed in mouse lungs and neutrophils and demonstrates anti-inflammatory properties in mouse lungs during acute lung injury, by inhibiting adherent neutrophil accumulation and inflammatory cytokine expression.

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Funding

Baljit Singh’s laboratory is supported with a Discovery Grant from Natural Sciences and Engineering Research Council of Canada. Funding for the laboratory of Suraj Unniappan is supported by an open operating grant from the Canadian Institutes of Health Research, an establishment grant from the Saskatchewan Health Research Foundation, John Evans Leaders Fund from the Canada Foundation for Innovation and from the University of Saskatchewan through the Centennial Enhancement Chair in Comparative Endocrinology. Gurpreet Aulakh's work is supported through Sylvia Fedoruk Centre for Nuclear Innovation Chair in Nuclear Imaging.

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Authors and Affiliations

  1. Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada

    Jasmine Hui, Suraj Unniappan & Baljit Singh

  2. Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada

    Gurpreet Kaur Aulakh

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  1. Jasmine Hui
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  2. Gurpreet Kaur Aulakh
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  3. Suraj Unniappan
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Correspondence to Baljit Singh.

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All applicable national guidelines for the care and use of animals were followed and all the experiments were approved by the Animal Ethics Board of University of Saskatchewan.

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Hui, J., Aulakh, G.K., Unniappan, S. et al. Loss of Nucleobindin-2/Nesfatin-1 increases lipopolysaccharide-induced murine acute lung inflammation. Cell Tissue Res 385, 87–103 (2021). https://doi.org/10.1007/s00441-021-03435-6

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