Abstract
Acute lung injury (ALI) is an acute failure of the respiratory system for which effective treatment is urgently necessary. Previous studies found that several peptides potently inhibited the production of cytokines induced by lipopolysaccharide (LPS). In this study, we synthetized a cell-permeable TIR domain-derived decoy peptide (TM6) and examined its substance for the ability to inhibit TLR signaling in the model of ALI induced by LPS. We demonstrated that TM6 (2.5, 5 and 10 nmol/g) alleviated the histological changes in the lung tissues as well as myeloperoxtidase (MPO) activity, lung W/D ratio, the production of TNF-α, IL-1β and IL-6 induced by LPS. Furthermore, the numbers of total cells, neutrophils and macrophages in the BALF were suppressed by TM6. In vitro, TM6 (5, 10 and 20 µM) inhibited the production of TNF-α, IL-1β and IL-6 in LPS-stimulated alveolar macrophages. Moreover, the activation of Nuclear factor-kappaB (NF-κB) and Mitogen activated protein kinases (MAPK) signaling pathways induced by LPS were also inhibited by TM6. Collectively, our results suggested that TM6 was an effective inhibitor of ALI induced by LPS, and this peptide may very well serve as a future treatment for ALI.
Highlights
Acute lung injury (ALI) has been recognized as a life-threatening disease, which is usually caused by pneumonia, sepsis, shock and aspiration[1, 2]
LPS could activate Toll like receptor 4 (TLR4), which subsequently induces the activation of NF-κB and Mitogen activated protein kinases (MAPK) signaling pathways[10, 11]
Pfalzraff A found that synthetic antimicrobial and LPS-neutralising peptides inhibited the production of inflammatory cytokines through inhibiting NF-κB and MAPK signaling pathway[16]
Summary
Acute lung injury (ALI) has been recognized as a life-threatening disease, which is usually caused by pneumonia, sepsis, shock and aspiration[1, 2]. Activation of TLR4 induces the accumulation of TIR domain-containing adapter protein, including MyD88, TRIAP, TRIF, and TRAM. Upon TLR4 activated, TRAM was served as a bridging adapter directly to recruit TRIF and render the production of cytokines. It has been suggested in some study that the recruitment of adapter proteins is through the interaction of TIR-TIR domains. We synthetized some TRAM TIR domain-derived decoy peptides and indicated that TM6 or TR6 inhibited the development of mastitis induced by LPS in mice[14, 15]. We investigated the therapeutic effects and mechanisms of TM6 on LPS-induced ALI both in vivo and in vitro
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
