GM-CSF production from human airway smooth muscle cells is potentiated by human serum

• Published in: Mediators of Inflammation Vol. 2000; no. 3-4; pp. 161 - 168
• Main Authors: Sukkar, M B, Hughes, J M, Johnson, P R, Armour, C L
• Format: Journal Article
• Language: English
• Published: United States Hindawi Limiteds 01.01.2000; Hindawi Limited
• Subjects: Asthma - blood; Asthma - etiology; Asthma - metabolism; Cells, Cultured; Cytokines - biosynthesis; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Humans; In Vitro Techniques; Inflammation Mediators - metabolism; Interleukin-1 - pharmacology; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Respiratory System - drug effects; Respiratory System - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Allergy; Human serum; TNF-a; GM-CSF; IL-5; Inflammation; IL-1b; Airway smooth muscle; Asthma
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1080/09629350020008673

RECENT evidence suggests that airway smooth muscle cells (ASMC) actively participate in the airway inflammatory process in asthma. Interleukin -1β (IL-1β) and tumour necrosis factor-α (TNF-α) induce ASMC to release inflammatory mediators in vitro. ASMC mediator release in vivo, however, may be influenced by features of the allergic asthmatic phenotype. We determined whether; (1) allergic asthmatic serum (AAS) modulates ASMC mediator release in response to IL-1β and TNF-α, and (2 ) IL-1β/TNF-α prime ASMC to release mediators in response to AAS. IL-5 and GMCSF were quantified by ELISA in culture supernatants of; (1) ASMC pre-incubated with either AAS, non allergic non-asthmatic serum (NAS) or Monomed^(TM) (a serum substitute ) and subsequently stimulated with IL-1β and TNF-α and (2 ) ASMC stimulated with IL-1β /TNF-α and subsequently ex posed to either AAS, NAS or Monomed^(TM). IL-1β and TNF-α induced GM-CSF release in ASMC pre-incubated with AAS was not greater than that in ASMC pr e-incubated with NAS or Monomed^(TM). IL-1β and TNF-α, however, primed ASMC to release GM-CSF in response to human se rum. GM-CSF production following IL-1β /TNF-α and serum exposure (AAS or NAS) was significantly greater than that following IL-1β /TNF-α and Monomed^(TM) exposure or IL-1β /TNF-α exposure only. Whilst the potentiating effects of human serum were not specific to allergic asthma, these findings suggest that the secretory capacity of ASMC may be up-regulated during exacerbations of asthma, where there is evidence of vascular leakage.