Toll-Like Receptor 4 (TLR4) is one of the receptors of innate immunity. It is activated by Pathogen- and Damage-Associated Molecular Patterns (PAMPs and DAMPs) and triggers pro-inflammatory responses that belong to the repertoire of innate immune responses, consequently protecting against infectious challenges and boosting adaptive immunity. Mild TLR4 stimulation by non-toxic molecules resembling its natural agonist (lipid A) provided efficient vaccine adjuvants.
Inhibition of the cluster of differentiation 14 innate immunity pathway with IAXO-101 improves chronic microelectrode performance
J Neural Eng. 15:025002 (2018). Hermann JK1, Ravikumar M, Shoffstall AJ, Ereifej ES, Kovach KM, Chang J, Soffer A, Wong C, Srivastava V, Smith P, Protasiewicz G, Jiang J, Selkirk SM, Miller RH, Sidik S, Ziats NP, Taylor DM, Capadona JR.
Neuroinflammatory mechanisms are hypothesized to contribute to intracortical microelectrode failures. The cluster of differentiation 14 (CD14) molecule is an innate immunity receptor involved in the recognition of pathogens and tissue damage to promote inflammation. The goal of the study was to investigate the effect of CD14 inhibition on intracortical microelectrode recording performance and tissue integration.
Sci Rep. 7:8623 (2017). Barboza R1, Lima FA2, Reis AS2, Murillo OJ2, Peixoto EPM2, Bandeira CL2, Fotoran WL2, Sardinha LR3, Wunderlich G2, Bevilacqua E4, Lima MRD5, Alvarez JM5, Costa FTM6, Gonçalves LA2, Epiphanio S7, Marinho CRF8.
Malaria-associated pregnancy has a significant impact on infant morbidity and mortality. The detrimental effects of malaria infection during pregnancy have been shown to correlate with immune activation in the placental tissue. Herein we sought to evaluate the effect of Toll-like receptors (TLRs) activation on placental malaria (PM) development by using the Plasmodium berghei NK65GFP infection model. We observed that activation of the innate immune system by parasites leads to PM due to local inflammation.
Effects of Toll-Like Receptor 4 Antagonists Against Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage in Mice
Toll-like receptor 4 (TLR4) signaling may play a crucial role in the occurrence of cerebral vasospasm after subarachnoid hemorrhage (SAH). The main purpose of this study was to assess if selective blockage of TLR4 on cerebral arteries prevents cerebral vasospasm development and neurological impairments after SAH in mice.
Synthetic and natural small molecule TLR4 antagonists inhibit motoneuron death in cultures from ALS mouse model (2016)
Pharmacol Res. 103:180 (2016). De Paola M1, Sestito SE2, Mariani A3, Memo C3, Fanelli R3, Freschi M4, Bendotti C4, Calabrese V2, Peri F5.
Increasing evidence indicates that inflammatory responses could play a critical role in the pathogenesis of motor neuron injury in amyotrophic lateral sclerosis (ALS). Recent findings have underlined the role of Toll-like receptors (TLRs) and the involvement of both the innate and adaptive immune responses in ALS pathogenesis.
Atherosclerosis. 242:563 (2015). Huggins C1, Pearce S1, Peri F2, Neumann F3, Cockerill G1, Pirianov G4.
The toll-like receptors (TLRs), including TLR4, have been shown to play a crucial role in vascular inflammatory diseases, such as atherosclerosis and aneurysm. The main goal of this study was to determine the potential of IAXO-102 (Innaxon, Tewkesbury), a novel small molecule TLR4 antagonist, to modulate non-hematopoietic TLR4 proinflammatory signalling and inhibit experimental abdominal aortic aneurysm (AAA) development.
Shah, D. Dhar, M. Jover, N.A. Davies, R.P. Mookerjee, R. Jalan UCL, Institute of Hepatology, London, UK
Without transplantation, about 40% of patients with acute liver failure (ALF) die. Its treatment is an unmet need. Unregulated inflammation plays an important role in the pathogenesis. Our hypothesis is that Toll like receptor 4 (TLR 4) is critical in the progression of inflammation in ALF. The aims of the study were to determine whether 1) administration of a novel TLR4 antagonist to an APAP model of ALF in mice would prevent liver injury. 2) TLR4 antagonist in ALF prolongs survival. 3) TLR4 KO are protected from the liver injury induced by acetaminophen (APAP).