Background: Inflammasomes are multimeric protein platforms involved in the regulation of inflammatory responses whose activity results in the production of proinflammatory cytokines. Because neuroinflammation is observed in autistic spectrum disorders (ASD), a neurologic condition of childhood resulting in a complex behavioural impairment, we analyzed the inflammasomes activity in ASD. Additionally we verified whether alterations of the gastrointestinal (GI) barriers might play a role in inflammasomes activation. Methods: The activity of the inflammasomes, the concentration of the inflammasomes-derived proinflammatory cytokines interleukin (IL)-1β and IL-18, and serum parameters of GI damage were analyzed in 25 ASD children, 23 healthy siblings (HS) and 30 unrelated age-matched healthy controls (HC). Results: A significant upregulation of the AIM2 and the NLRP3 inflammasomes and an increased production of IL-1β and IL-18 that was associated with a consistent reduction of IL-33, an anti inflammation cytokine were observed in ASD alone. Notably, in a possible immune-mediated attempt to dampen inflammation, IL-37, a suppressor of innate inflammatory responses, was significantly augmented in these same children. Finally, intestinal fatty acid binding protein (IFABP), an index of altered GI permeability, was significantly increased in serum of ASD and HS. Conclusions: These results show that the inflammasomes are activated in ASD and shed light on the molecular mechanisms responsible for ASD-associated neuroinflammation. The observation that GI alterations could be present as well in ASD offers a possible link between such alterations and neuroinflammation. Therapeutic strategies targeting inflammasome activation could be useful in ASD.

Multiple inflammasome complexes are activated in autistic spectrum disorders / M. Saresella, F. Piancone, I. Marventano, M. Zoppis, A. Hernis, M. Zanette, D. Trabattoni, M. Chiappedi, A. Ghezzo, M.P. Canevini, F. la Rosa, S. Esposito, M. Clerici. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 57(2016 Oct), pp. 125-133. [10.1016/j.bbi.2016.03.009]

Multiple inflammasome complexes are activated in autistic spectrum disorders

F. Piancone
Secondo
;
D. Trabattoni;M.P. Canevini;F. la Rosa;S. Esposito
Penultimo
;
M. Clerici
Ultimo
2016

Abstract

Background: Inflammasomes are multimeric protein platforms involved in the regulation of inflammatory responses whose activity results in the production of proinflammatory cytokines. Because neuroinflammation is observed in autistic spectrum disorders (ASD), a neurologic condition of childhood resulting in a complex behavioural impairment, we analyzed the inflammasomes activity in ASD. Additionally we verified whether alterations of the gastrointestinal (GI) barriers might play a role in inflammasomes activation. Methods: The activity of the inflammasomes, the concentration of the inflammasomes-derived proinflammatory cytokines interleukin (IL)-1β and IL-18, and serum parameters of GI damage were analyzed in 25 ASD children, 23 healthy siblings (HS) and 30 unrelated age-matched healthy controls (HC). Results: A significant upregulation of the AIM2 and the NLRP3 inflammasomes and an increased production of IL-1β and IL-18 that was associated with a consistent reduction of IL-33, an anti inflammation cytokine were observed in ASD alone. Notably, in a possible immune-mediated attempt to dampen inflammation, IL-37, a suppressor of innate inflammatory responses, was significantly augmented in these same children. Finally, intestinal fatty acid binding protein (IFABP), an index of altered GI permeability, was significantly increased in serum of ASD and HS. Conclusions: These results show that the inflammasomes are activated in ASD and shed light on the molecular mechanisms responsible for ASD-associated neuroinflammation. The observation that GI alterations could be present as well in ASD offers a possible link between such alterations and neuroinflammation. Therapeutic strategies targeting inflammasome activation could be useful in ASD.
autistic spectrum disorders (ASD); IFABP; inflammasome; neuroinflammation; NLRP3; immunology; behavioral neuroscience; endocrine and autonomic systems
Settore MED/38 - Pediatria Generale e Specialistica
Settore MED/04 - Patologia Generale
mar-2016
Article (author)
File in questo prodotto:
File Dimensione Formato  
SARESELLA inflammosome in autism 2016.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.27 MB
Formato Adobe PDF
1.27 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/428003
Citazioni
  • ???jsp.display-item.citation.pmc??? 22
  • Scopus 51
  • ???jsp.display-item.citation.isi??? 49
social impact