作者
L Al-Alwan, Y Chang, C Baglole, A Halayko, J Martin, D Eidelman, Q Hamid, J Johnson, S Audusseau, M Lamontagne, C Couture, M Laviolette, Y Bossé, M Morissette, P Shen, D Bowdish, M Stampfli, J Bérubé, É Lavoie-Charland, N Gaudreault, L Boulet, W Davidson, L Dauncey, L Dueck, R Schreiner, D Bakal, S Kirychuk, J Lawson, R Bryce, P Pahwa, C Karunanayake, D Rennie, L Hagel, J Dosman, T To, S Stanojevic, S Dell, D Lougheed, H Zheng, J Zhu, L Feldman, J Simatovic, A Gershon, P Camp, D Marciniuk, M Doucet, R Prosser, A Kozyrskj, N Garvey, K Reimer, S Vanderloo, C Gilbert, L McRae, A Kirkham, C Sima, E Chan-Thim, V Pepin, G Moullec, C Duclos, A Rizk, J Paquet, M Dumont, T Janaudis-Ferreira, P Robles, M Beauchamp, R Goldstein, D Brooks, L D’Souza, R Wardini, M de Lorimier, S Bacon, K Lavoie, S Parenteau, F Beaucage, R Foty, C Licskai, T Alahmadi, D Zielinski, R Troini, M Kaminska, M Guez, G Rakovich, M Tardif, C Claveau, T Larsen, D Lucy, K Choong, K Koo, M Yeung, M Ferrone, A Taite, C Madeley, A Lavigne, J Cafazzo, A Mesbah, F Marquis, C Sirois, Y Bendavid, A Babayan, R Schwartz, S Zarins, S Athron, M Lougheed, J Olajos-Clow, F Ducharme, M Jabbour, L Desveaux, M Gagné, V Émond, A Kitchlu, T Abdelshaheed, E Tullis, S Gupta, S Martin, S Bornstein, S Small, A Butt, P Demers, E Dicks, G Farrell, K Fowler, G Fox, T Murphy, B Neis, J Oudyk, T Takaro, K Kam, M McKay, M Witmans, J MacLean, S Spier, I Mitchell, B Paes, A Li, K Lanctôt, V Coats, J Lalancette, Y Lacasse, F Maltais, D Saey, L Wickerson, S Mathur, D Helm, L Singer, M Mura, Y Zhao, Z Yun, S Keshavjee, M de Perrot, J Granton
发表日期
2013/1/1
期刊
Canadian Respiratory Journal
卷号
20
期号
3
页码范围
e60-e81
简介
METHODS:
High-fold concentrations (0.01, 0.1, 1, 10 and 100 ng/ml) and low-fold concentrations (0.25, 0.5, 1, 2 and 4 ng/ml) of recombinant human GRO-α were used to assess ASMC migration using a modified Boyden chamber. The mechanism by which GRO-α regulates ASMC migration was investigated, firstly; by assessing the receptor (s) mediating this effect either by use of neutralizing antibodies or siRNA knock-down and secondly; by utilizing pharmacological inhibitors we examined the signaling pathways activated by these receptors.
RESULTS:
At high-fold concentrations GRO-α has no effect on ASMC migration; however, when using the low-dose concentrations, at 2 and 4 ng/ml, GRO-α appeared to exhibit an inhibitory effect on ASMC migration. When investigating the receptor mediating the inhibitory effect of GRO-α on ASMC migration, we found it to be mediated through the decoy receptor ‘Duffy antigen receptor for chemokines’(DARC), but not CXCR1 nor CXCR2. Finally, we established ERK 1/2 MAPK as the signaling pathway responsible in mediating GROα inhibition of ASMC migration
CONCLUSION:
Unlike the common notion of chemokines function as inducers of cell migration, we established GRO-α as a negative regulator of ASMC migration. An effect that was mediated DARC receptor and ERK 1/2 MAPK pathway. These results suggest that GRO-α/DARC axis may be a potential target of therapy in diseases where inordinate cell migration plays a central role.
RATIONALE:
There is little information on the characteristics of physical inactivity in individuals hospitalized with an acute exacerbation of COPD (AECOPD). We …
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L Al-Alwan, Y Chang, C Baglole, A Halayko, J Martin… - Canadian Respiratory Journal, 2013