A therapeutic oxygen carrier isolated from Arenicola marina decreased P. gingivalis induced inflammation and tissue destruction

Abstract

The control of inflammation and infection is crucial for periodontal wound healing and regeneration. M101, an oxygen carrier derived from Arenicola marina, was tested for its anti-inflammatory and anti-infectious potential based on its anti-oxidative and tissue oxygenation properties. In vitro, no cytotoxicity was observed in oral epithelial cells (EC) treated with M101. M101 (1 g/L) reduced significantly the gene expression of pro-inflammatory markers such as TNF-α, NF-κΒ and RANKL in P. gingivalis-LPS stimulated and P. gingivalis-infected EC. The proteome array revealed significant down-regulation of pro-inflammatory cytokines (IL-1β and IL-8) and chemokine ligands (RANTES and IP-10), and upregulation of pro-healing mediators (PDGF-BB, TGF-β1, IL-10, IL-2, IL-4, IL-11 and IL-15) and, extracellular and immune modulators (TIMP-2, M-CSF and ICAM-1). M101 significantly increased the gene expression of Resolvin-E1 receptor. Furthermore, M101 treatment reduced P. gingivalis biofilm growth over glass surface, observed with live/dead analysis and by decreased P. gingivalis 16 s rRNA expression (51.7%) (p < 0.05). In mice, M101 reduced the clinical abscess size (50.2%) in P. gingivalis-induced calvarial lesion concomitant with a decreased inflammatory score evaluated through histomorphometric analysis, thus, improving soft tissue and bone healing response. Therefore, M101 may be a novel therapeutic agent that could be beneficial in the management of P. gingivalis associated diseases.

Oral Microbiota: A Major Player in the Diagnosis of Systemic Diseases

“…Next to AMPs, other fields are investigated, and recently, an oxygen transporter derived from the marine lugworm Arenicola marina, HEMARINA-M101 (M101), was tested. M101's anti-inflammatory and anti-infectious potential, based on its anti-oxidative and tissue oxidation properties, have been tested in vitro on biofilm cultures containing Pg and in vivo in a Pg-induced subcutaneous calvarial abscess in a mouse model [271]. The results showed that M101 significantly reduced the release of pro-inflammatory cytokines and also had an anti-bacterial effect on Pg, confirming its pro-healing properties and making it a potential therapeutic agent in periodontal wound healing and regeneration [271].…”

Humanized Mouse Models for the Study of Periodontitis: An Opportunity to Elucidate Unresolved Aspects of Its Immunopathogenesis and Analyze New Immunotherapeutic Strategies

“…( [55][56][57][58] mice (70). Besides, the removal of ligatures allows the study of lesion healing and resolution of inflammation (53).…”

The Potential Role of RP105 in Regulation of Inflammation and Osteoclastogenesis During Inflammatory Diseases

“… Proinflammatory cytokines regulate osteoclastogenesis via direct interaction with their receptors. Proinflammatory cytokines such as IL-1β, IL-6, IL-17, and TNF-α secreted by different immune cells induce RANKL production in endothelial cells ( Batool et al, 2020 ), fibroblasts ( Nagasawa et al, 2007 ; Hienz et al, 2015 ), and osteoblast lineage cells ( Algate et al, 2016 ). OPG, secreted by osteoblast, works as a decoy receptor of RANKL to negatively regulate osteoclastogenesis ( Lam et al, 2000 ).…”

“…RANKL commits the cells to the osteoclastic lineage and TNF-α ensures the induction of differentiation through TNF-α receptor (TNFR) signaling, suggesting a synergistic relationship between RANKL and TNF-α ( Fuller et al, 2002 ). In contrast, LPS/TLR4 signaling initiates RANKL-dependent osteoclastogenesis partially by promoting RANKL production in osteoblasts ( Algate et al, 2016 ), gingival fibroblasts ( Nagasawa et al, 2007 ; Hienz et al, 2015 ), oral epithelial cells ( Batool et al, 2020 ), and DCs ( Alnaeeli et al, 2007 ). Inhibition of TLR4 and TLR2 in osteoblasts results in decreased RANKL expression even after exposure to LPS ( Tang et al, 2011 ).…”