The Novel Human β-Defensin 114 Regulates Lipopolysaccharide (LPS)-mediated Inflammation and Protects Sperm from Motility Loss

Abstract

Background: Human ␤-defensins are predominantly expressed in the male reproductive system, but their functions remain unknown. Results: Recombinant human DEFB114 rescues human sperm motility and D-GalN-sensitized mice under LPS challenges through its LPS-neutralizing activity. Conclusion: Recombinant DEFB114 peptides have therapeutic potential for LPS-induced inflammatory diseases.Significance: This work contributes to unveiling novel functions of human ␤-defensins that are crucial for addressing their physiological and pathological mechanisms.

Highly stable aptamers selected from a 2′-fully modified fGmH RNA library for targeting biomaterials

“…Due to its higher throughput, greater automation, and lower cost compared to other methods of affinity detection, BLI has been applied in the study of more and more molecular interactions [52–54]. BLI assays were run at 30 °C on an Octet QK using Protein A (ProA) biosensors (Pall ForteBio Corp., Menlo Park, CA) and black 96-well microplates.…”

Antimicrobial Peptides in Host Defense: Functions Beyond Antimicrobial Activity

“…Antimicrobial peptides readily bind to microbial lipopolysaccharides, adhesins, and toxins with rapid association rate constants, slower dissociation rate constants, and high affi nity (Caccavo et al 2002 ;Wang et al 2003Wang et al , 2006Owen et al 2004a , b ;Liu et al 2013a ;Yu et al 2013 ;Dietrich et al 2008 ;Pingel et al 2008 ). This binding generally alters the physiological properties of the agonist (Gough et al 1996 ;Motzkus et al 2006 ;Scott et al 2011 ;Kim et al 2005Kim et al , 2006Giesemann et al 2008 ;Yeom et al 2011 ).…”

“…HNP-1 attenuates an LPS-induced IL-1β, but not TNF-α, response in human monocytes (Shi et al 2007 ); DEFA1-3 attenuates P. aeruginosa -induced TNF-α, IL-8, IL-6, and IL-1β responses in human monocyte-derived macrophages (Miles et al 2009 ); and HNP-1 and HNP-3 attenuate P. intermedia LPS-induced IL-1β, IL-8, and ICAM-1 responses in THP-1 human monocytes and HGF cells (Lee et al 2010 ). HBD1, HBD2, HBD3, and DEFB104A attenuate P. intermedia LPS-induced IL-1β, IL-8, and ICAM-1 responses in THP-1 human monocytes and HGF cells (Lee et al 2010 ); HBD3 attenuates the IL-6, IL-10, GM-CSF, and TNF-α responses of HagB-induced human myeloid dendritic cells (Pingel et al 2008 ); DEFB114 attenuates an LPS-induced TNF-α response in RAW264.7 murine macrophages (Yu et al 2013 ); and DEFB123 (Motzkus et al 2006 ) and DEFB126 (Liu et al 2013a ) attenuate an LPS-induced IL-6 (e.g., DEFB126) and TNF-α (e.g., DEFB123, DEFB126) response in RAW264.7 murine macrophages. Finally, θ-defensin retrocyclin RTD-1 inhibits a TLR2, 4, and 5 agonist-induced TNF-α, IL-1α, IL-1β, IL-6, IL-8, MCP-1 (CCL2), MIP-1α (CCL3), and MIP-1β (CCL4) responses in human peripheral blood leukocytes (Schaal et al 2012 ).…”

“…Antimicrobial peptides can selectively attenuate agonist-induced signal transduction including MAPK pathways involving p38, c-Jun NH 2 -terminal protein kinases (JNK), or extracellular signal-regulated kinase (ERK). DEFB114 attenuates an LPS-induced activation of p42/44 responses in RAW264.7 murine macrophages (Yu et al 2013 ), and DEFB123 (Motzkus et al 2006 ) and DEFB126 (Liu et al 2013a ) attenuate an LPS-induced activation of p42/44 and p38 responses in RAW264.7 murine macrophages. LL-37 attenuates a P. gingivalis extract-induced activation of p38 and ERK responses in human gingival fi broblasts (Inomata et al 2010 ).…”

“…Attenuates agonist-induced, chemokine, and proinfl ammatory cytokine responses in macrophages (Scott et al 2000 ), lung epithelial cells (Scott et al 2000 ), peripheral blood mononuclear cells (Molhoek et al 2009 ), and whole blood leukocytes (Walters et al 2010 ) Attenuates MAPK pathway activation of p38 and ERK responses in gingival fi broblasts (Inomata et al 2010 ) α -defensins Inhibit the production of proinfl ammatory cytokines from macrophages (Miles et al 2009 ) Attenuate a chemokine and proinfl ammatory cytokine response in mice (Kohlgraf et al 2010 ) β -defensins HBD3 attenuates agonist-induced, chemokine, and proinfl ammatory cytokine responses in dendritic cells (Pingel et al 2008 ;Harvey et al 2013 ), in THP-1 human myelomonocytic cells (Semple et al 2010 ), peripheral blood monocyte-derived macrophages (Semple et al 2010 ), and in RAW264.7 murine macrophages (Semple et al 2010 ) DEFB114 attenuates MAPK pathway p42/44 response and attenuates an agonist-induced TNF-α response in RAW264.7 murine macrophages (Yu et al 2013 ) DEFB123 attenuates an agonist-induced MAPK pathway activation of p42/44 and p38 and attenuates an agonist-induced TNF-α response in RAW264.7 murine macrophages (Motzkus et al 2006 ) DEFB126 attenuates an agonist-induced proinfl ammatory response in RAW264.7 murine macrophages (Liu et al 2013a ) Attenuate a chemokine and proinfl ammatory cytokine response in mice (Kohlgraf et al 2010 ) θ-defensins Retrocyclin RTD-1 attenuates agonist-induced, chemokine, and proinfl ammatory cytokine responses in human peripheral blood leukocytes (Schaal et al 2012 …”