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Modulation of proinflammatory activity by the engineered cationic antimicrobial peptide WLBU-2

Paranjape, SM and Lauer, TW and Montelaro, RC and Mietzner, TA and Vij, N (2013) Modulation of proinflammatory activity by the engineered cationic antimicrobial peptide WLBU-2. F1000Research, 2. ISSN 2046-1402

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Abstract

© 2013 Paranjape SM et al. Background: Host-derived (LL-37) and synthetic (WLBU-2) cationic antimicrobial peptides (CAPs) are known for their membrane-active bactericidal properties. LL-37 is an important mediator for immunomodulation, while the mechanism of action of WLBU-2 remains unclear. Objective: To determine if WLBU-2 induces an early proinflammatory response that facilitates bacterial clearance in cystic fibrosis (CF). Methods: C57BL6 mice were given intranasal or intraperitoneal 1×10 6 cfu/mL Pseudomonas aeruginosa (PA) and observed for 2h, followed by instillation of LL-37 or WLBU-2 (2-4mg/kg) with subsequent tissue collection at 24h for determination of bacterial colony counts and quantitative RT-PCR measurement of cytokine transcripts. CF airway epithelial cells (IB3-1, F508/W1282X) were cultured in appropriate media with supplements. WLBU-2 (25μM) was added to the media with RT-PCR measurement of TNF-α and IL-1βtranscripts after 20, 30, and 60min. Flow cytometry was used to determine if WLBU-2 assists in cellular uptake of Alexa 488-labeled LPS. Results: In murine lung exposed to intranasal or intraperitoneal WLBU-2, there was a reduction in the number of surviving PA colonies compared to controls. Murine lung exposed to intraperitoneal WLBU-2 showed fewer PA colonies compared to LL-37. After 24h WLBU-2 exposure, PA-induced IL-1βtranscripts from lungs showed a twofold decrease (p&0.05), while TNF-α levels were unchanged. LL-37 did not significantly change transcript levels. In IB3-1 cells, WLBU-2 exposure resulted in increased TNF-α and IL-1βtranscripts that decreased by 60min. WLBU-2 treatment of IB3-1 cells displayed increased LPS uptake, suggesting a potential role for CAPs in inducing protective proinflammatory responses. Taken together, the cytokine response, LPS uptake, and established antimicrobial activity of WLBU-2 demonstrate its ability to modulate proinflammatory signaling as a protective mechanism to clear infection. Conclusions: The immunomodulatory properties of WLBU-2 reveal a potential mechanism of its broad-spectrum antibacterial activity and warrant further preclinical evaluation to study bacterial clearance and rescue of chronic inflammation.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Paranjape, SM
Lauer, TW
Montelaro, RCrmont@pitt.eduRMONT
Mietzner, TA
Vij, N
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
ReviewerNijnik, AnastasiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
ReviewerSavage, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 8 February 2013
Date Type: Publication
Journal or Publication Title: F1000Research
Volume: 2
DOI or Unique Handle: 10.12688/f1000research.2-36.v1
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
ISSN: 2046-1402
Date Deposited: 08 Aug 2016 17:45
Last Modified: 04 Feb 2019 15:57
URI: http://d-scholarship.pitt.edu/id/eprint/29133

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