Epithelium-derived chemokines induce airway smooth muscle cell migration.
BACKGROUND
The remodelling of airway smooth muscle (ASM) associated with asthma severity may involve the migration of ASM cells towards the epithelium. However, little is known about the mechanisms of cell migration and the effect of epithelial-derived mediators on this process.


OBJECTIVE
The main objective of the current study is to assess the effects of epithelial-derived chemokines on ASM cell migration.


METHODS
Normal human ASM cells were incubated with supernatants from cells of the bronchial epithelial cell line BEAS-2B and normal human bronchial epithelial (NHBE) cells. To induce chemokine production, epithelial cells were treated with TNF-alpha. Chemokine expression by epithelial cells was evaluated by quantitative real-time PCR, ELISA and membrane antibody array. To identify the role of individual chemokines in ASM cell migration, we performed migration assays with a modified Boyden chamber using specific neutralizing antibodies to block chemokine effects.


RESULTS
Supernatants from BEAS-2B cells treated with TNF-alpha increased ASM cell migration; migration was increased 1.6 and 2.5-fold by supernatant from BEAS-2B cells treated with 10 and 100 ng/mL TNF-alpha, respectively. Protein levels in supernatants and mRNA expression by BEAS-2B cells of regulated on activation, normal T cell expressed and secreted (RANTES) and IL-8 were significantly increased by 100 ng/mL TNF-alpha treatment. The incubation of supernatant with antibodies to RANTES or IL-8 significantly reduced ASM cell migration, and the combined antibodies further inhibited the cell migration. The migratory effects of supernatants and inhibiting effects of RANTES and/or IL-8 were confirmed also using NHBE cells.


CONCLUSIONS
The results show that chemokines from airway epithelial cells cause ASM cell migration and might potentially play a role in the process of airway remodelling in asthma.
Takeda
N
N
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Sumi
Y
Y
Préfontaine
D
D
Al Abri
J
J
Al Heialy
N
N
Al-Ramli
W
W
Michoud
M-C
MC
Martin
J G
JG
Hamid
Q
Q
D001980:Bronchi / Q000166:cytology* / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D004848:Epithelium / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D018946:Chemokine CCL5; D018925:Chemokines; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha