In:
The Journal of Immunology, The American Association of Immunologists, Vol. 208, No. 12 ( 2022-06-15), p. 2795-2805
Abstract:
Defensins are a major class of antimicrobial peptides that facilitate the immune system to resist pathogen infection. To date, only β-defensins have been identified in pigs. In our previous studies, porcine β-defensin 2 (PBD-2) was shown to have both bactericidal activity and modulatory roles on inflammation. PBD-2 can interact with the cell surface TLR4 and interfere with the NF-κB signaling pathway to suppress the inflammatory response. In this study, the intracellular functions of PBD-2 were investigated. The fluorescently labeled PBD-2 could actively enter mouse macrophage cells. Proteomic analysis indicated that 37 proteins potentially interacted with PBD-2, among which vasohibin-1 (VASH1) was further tested. LPS, an inflammation inducer, suppressed the expression of VASH1, whereas PBD-2 inhibited this effect. PBD-2 inhibited LPS-induced activation of Akt, expression and release of the inflammatory mediators vascular endothelial growth factor and NO, and cell damage. A follow-up VASH1 knockdown assay validated the specificity of the above observations. In addition, PBD-2 inhibited LPS-induced NF-κB activation via Akt. The inhibition effects of PBD-2 on LPS triggered suppression of VASH1 and activation of Akt, and NF-κB and inflammatory cytokines were also confirmed using pig alveolar macrophage 3D4/21 cells. Therefore, the data indicate that PBD-2 interacts with intracellular VASH1, which inhibits the LPS-induced Akt/NF-κB signaling pathway, resulting in suppression of inflammatory responses. Together with our previous findings, we conclude that PBD-2 interacts with both the cell surface receptor (TLR4) and also with the intracellular receptor (VASH1) to control inflammation, thereby providing insights into the immunomodulatory roles of defensins.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.2100810
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2022
detail.hit.zdb_id:
1475085-5
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