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Secretory Leucoprotease Inhibitor (SLPI) Promotes Survival during Acute Pseudomonas aeruginosa Infection by Suppression ofInflammation Rather than Microbial Killing
Osbourn, M.; Rodgers, A.M.; Dubois, A.V.; Small, D.M.; Humphries, F.; Delagic, N.; Moynagh, P.N.; Weldon, S.; Taggart, C.C.; Ingram, R.J. Secretory Leucoprotease Inhibitor (SLPI) Promotes Survival during Acute Pseudomonas aeruginosa Infection by Suppression of Inflammation Rather Than Microbial Killing. Biomolecules2022, 12, 1728.
Osbourn, M.; Rodgers, A.M.; Dubois, A.V.; Small, D.M.; Humphries, F.; Delagic, N.; Moynagh, P.N.; Weldon, S.; Taggart, C.C.; Ingram, R.J. Secretory Leucoprotease Inhibitor (SLPI) Promotes Survival during Acute Pseudomonas aeruginosa Infection by Suppression of Inflammation Rather Than Microbial Killing. Biomolecules 2022, 12, 1728.
Osbourn, M.; Rodgers, A.M.; Dubois, A.V.; Small, D.M.; Humphries, F.; Delagic, N.; Moynagh, P.N.; Weldon, S.; Taggart, C.C.; Ingram, R.J. Secretory Leucoprotease Inhibitor (SLPI) Promotes Survival during Acute Pseudomonas aeruginosa Infection by Suppression of Inflammation Rather Than Microbial Killing. Biomolecules2022, 12, 1728.
Osbourn, M.; Rodgers, A.M.; Dubois, A.V.; Small, D.M.; Humphries, F.; Delagic, N.; Moynagh, P.N.; Weldon, S.; Taggart, C.C.; Ingram, R.J. Secretory Leucoprotease Inhibitor (SLPI) Promotes Survival during Acute Pseudomonas aeruginosa Infection by Suppression of Inflammation Rather Than Microbial Killing. Biomolecules 2022, 12, 1728.
Abstract
Secretory leucoprotease inhibitor (SLPI) has multifaceted functions, including inhibition of protease activity, antimicrobial functions, and anti-inflammatory properties. In this study, we show that SLPI plays a role in controlling pulmonary P. aeruginosa infection. Mice lacking SLPI were highly susceptible to P. aeruginosa infection, however had no difference in bacterial burden. Utilising a model of P. aeruginosa LPS-induced lung inflammation, human recombinant SLPI (hrSLPI) administered intraperitoneally suppressed the recruitment of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and resulted in reduced BALF and serum levels of inflammatory cytokines and chemokines. This anti-inflammatory effect of hrSLPI was similarly demonstrated in a systemic inflammation model induced by intraperitoneal injection of LPS from various bacteria or lipoteichoic acid, highlighting the broad anti-inflammatory properties of hrSLPI. Moreover, in bone-marrow-derived macrophages, hrSLPI reduced LPS-induced phosphorylation of p-IkB-α, p-IKK-α/β, p-P38, demonstrating that the anti-inflammatory effect of hrSLPI was due to the inhibition of the NFB and MAPK pathways. In conclusion, administration of hrSLPI attenuates excessive inflammatory responses and is therefore, a promising strategy to target inflammatory diseases such as acute respiratory distress syndrome or sepsis and could potentially be used to augment antibiotic treatment.
Medicine and Pharmacology, Medicine and Pharmacology
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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