scholarly journals Modulation of Vagal Sensory Neurons via High Mobility Group Box-1 and Receptor for Advanced Glycation End Products: Implications for Respiratory Viral Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Stuart B. Mazzone ◽  
Seung-Kwon Yang ◽  
Jennifer A. Keller ◽  
Juste Simanauskaite ◽  
Jaisy Arikkatt ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Sensory Neuron ◽  
Sensory Neurons ◽  
Advanced Glycation End Products ◽  
High Mobility ◽  
High Mobility Group ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Deficient Mice

Vagal sensory neurons contribute to the symptoms and pathogenesis of inflammatory pulmonary diseases through processes that involve changes to their morphological and functional characteristics. The alarmin high mobility group box-1 (HMGB1) is an early mediator of pulmonary inflammation and can have actions on neurons in a range of inflammatory settings. We hypothesized that HMGB1 can regulate the growth and function of vagal sensory neurons and we set out to investigate this and the mechanisms involved. Culturing primary vagal sensory neurons from wildtype mice in the presence of HMGB1 significantly increased neurite outgrowth, while acute application of HMGB1 to isolated neurons under patch clamp electrophysiological investigation produced inward currents and enhanced action potential firing. Transcriptional analyses revealed the expression of the cognate HMGB1 receptors, Receptor for Advanced Glycation End products (RAGE) and Toll-like Receptor 4 (TLR4), in subsets of vagal sensory neurons. HMGB1-evoked growth and electrophysiological responses were significantly reduced in primary vagal sensory neurons harvested from RAGE deficient mice and completely absent in neurons from RAGE/TLR4 double deficient mice. Immunohistochemical analysis of vagal sensory neurons collected from mice after intranasal infection with murine pneumovirus or influenza A virus (IAV), or after intratracheal administration with the viral mimetic PolyI:C, revealed a significant increase in nuclear-to-cytoplasm translocation of HMGB1 compared to mock-inoculated mice. Neurons cultured from virus infected wildtype mice displayed a significant increase in neurite outgrowth, which was not observed for neurons from virus infected RAGE or RAGE/TLR4 deficient mice. These data suggest that HMGB1 can enhance vagal sensory neuron growth and excitability, acting primarily via sensory neuron RAGE. Activation of the HMGB1-RAGE axis in vagal sensory neurons could be an important mechanism leading to vagal hyperinnervation and hypersensitivity in chronic pulmonary disease.

scholarly journals High-mobility group box 1 inhibits HCO3− absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway

2015 ◽  
Vol 309 (8) ◽  
pp. F720-F730 ◽  
Author(s):  
David W. Good ◽  
Thampi George ◽  
Bruns A. Watts
Keyword(s):  
Advanced Glycation End Products ◽  
Basolateral Membrane ◽  
High Mobility ◽  
High Mobility Group ◽  
Renal Tubules ◽  
Thick Ascending Limb ◽  
Advanced Glycation ◽  
Medullary Thick Ascending Limb ◽  
Glycation End Products ◽  
End Products

High-mobility group box 1 (HMGB1) is a damage-associated molecule implicated in mediating kidney dysfunction in sepsis and sterile inflammatory disorders. HMGB1 is a nuclear protein released extracellularly in response to infection or injury, where it interacts with Toll-like receptor 4 (TLR4) and other receptors to mediate inflammation. Previously, we demonstrated that LPS inhibits HCO3- absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-ERK pathway (Watts BA III, George T, Sherwood ER, Good DW. Am J Physiol Cell Physiol 301: C1296–C1306, 2011). Here, we examined whether HMGB1 could inhibit HCO3- absorption through the same pathway. Adding HMGB1 to the bath decreased HCO3− absorption by 24% in isolated, perfused rat and mouse MTALs. In contrast to LPS, inhibition by HMGB1 was preserved in MTALs from TLR4−/− mice and was unaffected by ERK inhibitors. Inhibition by HMGB1 was eliminated by the receptor for advanced glycation end products (RAGE) antagonist FPS-ZM1 and by neutralizing anti-RAGE antibody. Confocal immunofluorescence showed expression of RAGE in the basolateral membrane domain. Inhibition of HCO3−absorption by HMGB1 through RAGE was additive to inhibition by LPS through TLR4 and to inhibition by Gram-positive bacterial molecules through TLR2. Bath amiloride, which selectively prevents inhibition of MTAL HCO3− absorption mediated through Na+/H+ exchanger 1 (NHE1), eliminated inhibition by HMGB1. We conclude that HMGB1 inhibits MTAL HCO3− absorption through a RAGE-dependent pathway distinct from TLR4-mediated inhibition by LPS. These studies provide new evidence that HMGB1-RAGE signaling acts directly to impair the transport function of renal tubules. They reveal a novel paradigm for sepsis-induced renal tubule dysfunction, whereby exogenous pathogen-associated molecules and endogenous damage-associated molecules act directly and independently to inhibit MTAL HCO3− absorption through different receptor signaling pathways.

Role of Receptors for Advanced Glycation End Products and High-Mobility Group Box 1 in the Outcome of Human T Cell Lymphotropic Type 1 Infection

2019 ◽  
Vol 32 (2) ◽  
pp. 89-94 ◽  
Author(s):  
Nafise Yaghouti ◽  
Reza Boostani ◽  
Asadollah Mohamamdi ◽  
Zohreh Poursina ◽  
Seyed Abdolrahim Rezaee ◽  
...  
Keyword(s):  
T Cell ◽  
Advanced Glycation End Products ◽  
High Mobility ◽  
High Mobility Group ◽  
Advanced Glycation ◽  
Human T Cell ◽  
Glycation End Products ◽  
End Products

Stimulation of erythroleukaemia cell differentiation by extracellular high-mobility group-box protein 1 is independent of the receptor for advanced glycation end-products

2002 ◽  
Vol 363 (3) ◽  
pp. 529-535 ◽  
Author(s):  
Bianca SPARATORE ◽  
Marco PEDRAZZI ◽  
Mario PASSALACQUA ◽  
Deborah GAGGERO ◽  
Mauro PATRONE ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Advanced Glycation End Products ◽  
High Mobility ◽  
Cell Types ◽  
Dominant Negative ◽  
High Mobility Group ◽  
Advanced Glycation ◽  
Stable Transfectants ◽  
Glycation End Products ◽  
End Products

In several cell types the binding of extracellular high-mobility group-box protein 1 (HMGB1) with the receptor for advanced glycation end-products (RAGE) induces cytoskeletal reorganization and cell motility. To establish whether RAGE is also involved in murine erythroleukaemia (MEL) cell differentiation stimulated by HMGB1, we have demonstrated that these cells express a 51kDa protein identified as RAGE, and then we have produced stable transfectants overexpressing wild-type (wt) RAGE or a dominant negative (dn) RAGE mutant lacking the cytoplasmic domain to analyse the differentiation process in these cells. Several experimental findings indicated that RAGE was not involved in the MEL cell differentiation programme. This was also supported by the identical stimulatory effect exerted by HMGB1 on both wt- or dn-RAGE transfectants. We have also observed that HMGB1 binds a 65kDa protein on the surface of MEL cells, supporting the hypothesis that alternative targets of HMGB1 are expressed on the MEL cell membrane and may be involved as mediators of its signalling.

Sign in / Sign up

Export Citation Format

Share Document