ABSTRACT
Type-2 immunity elicits tissue repair and homeostasis, however dysregulated type-2 responses cause aberrant tissue remodelling, as observed in asthma. Severe respiratory viral infections in infancy predispose to later asthma, however, the processes that mediate tissue damage-induced type-2 inflammation and the origins of airway remodelling remain ill-defined. Here, using a preclinical mouse model of viral bronchiolitis, we find that increased epithelial and mesenchymal high-mobility group box 1 (HMGB1) expression is associated with increased numbers of IL-13-producing type-2 innate lymphoid cell (ILC2s) and the expansion of the airway smooth muscle (ASM) layer. Anti-HMGB1 ablated lung ILC2 numbers and ASM growth in vivo, and inhibited ILC2-mediated ASM cell proliferation in a co-culture model. Furthermore, we identified that HMGB1/RAGE (receptor for advanced glycation endproducts) signalling mediates an ILC2-intrinsic IL-13 auto-amplification loop. In summary, therapeutic targeting of the HMGB1/RAGE signalling axis may act as a novel asthma preventative by dampening ILC2-mediated type-2 inflammation and associated ASM remodelling.
Subject(s)
Airway Remodeling/immunology , HMGB1 Protein/immunology , Inflammation/immunology , Lymphocytes/immunology , Muscle, Smooth/immunology , Animals , Mice , Muscle, Smooth/pathology , Receptor for Advanced Glycation End Products/immunologyABSTRACT
In the present study the in vitro antimicrobial activity, along with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), of different extracts of leaves of Mesua nagassarium were evaluated against 13 pathogenic microorganisms. The methanol extract and its pet-ether and carbon tetrachloride soluble fractions showed the highest antimicrobial activity. The carbon tetrachloride soluble fraction showed the maximum inhibition zone of 24.33 mm against Bacillus megaterium with MIC and MBC values of 7.81 ug/ml and 250 ug/ml, respectively. Ciprofloxacin (30 ug/disc) was used as standard antimicrobial agent. In the Brine shrimp lethality bioassay, the crude methanol extract and its carbon tetrachloride soluble fraction showed significant cytotoxicity with LC50 of 2.99 and 1.74 ug/ml, respectively as compared vincristine sulphate (LC50 value 0.543 ug/ml).
En el presente estudio se evaluó la actividad antimicrobiana in vitro, incluyendo la concentración inhibitoria mínima (CIM) y la concentración bactericida mínima (CBM), de diferentes extractos obtenidos de hojas de Mesua nagassarium en 13 microorganismos patógenos. El extracto metanólico y sus fracciones solubles en éter de petróleo y tetracloruro de carbono, mostraron la mayor actividad antimicrobiana. La fracción de compuestos solubles en tetracloruro de carbono mostró la zona de inhibición máxima de 24.33 mm en Bacillus megaterium con valores de CIM y and CBM de 7.81 ug/ml y 250 ug/ml, respectivamente. Como agente antimicrobiano estándar se utilizó ciprofloxacina (30 ug/disco). En el bioensayo de mortalidad de Brine shrimp el extracto metanólico y su fracción soluble en tetracloruro de carbono mostraron importante citotoxicidad con CL50 de 2.99 y 1.74 ug/ml, respectivamente, comparadas con el sulfato de vincristina (CL50 0.543 ug/ml).
