Accueil du site > Production scientifique > The disulfide bond between cysteine 10 and cysteine 34 is required for CCL18 activity.
Date de publication: 1er octobre 2013
B. Legendre, C. Tokarski, Y. Chang, N. De Freitas Caires, H. Lortat-Jacob, P. D. Nadaï, C. Rolando, C. Duez, A. Tsicopoulos, P. Lassalle.
Cytokine 64 463-470 (2013). DOI
Travail réalisé sur le site de l’Université de Lille 1, Sciences et Technologies.
Asthma is a Th2-mediated disease that involves Th2 cell and eosinophil migration into the bronchial mucosa which is dependent upon the expression of a specific set of chemokines within the lung. Among them, CCL18 seems to play a key role because of its preferential expression in the lung, and its up-regulation by Th2 cytokines. Here, we show that the optimal naïve T cell and basophil chemotaxis, and basophil histamine release induced by rhCCL18 occurred at a 100 time lower concentration with CHO-derived rhCCL18 than with E. coli-derived rhCCL18. FT-ICR mass spectrometry of the intact chemokines showed that the rhCCL18 produced by CHO cells contained the 2 disulfide bonds Cys10-Cys34 and Cys11-Cys50, in clear contrast to the rhCCL18 derived from E. coli where the Cys10-Cys34 bond was absent. We found that reduction of the Cys10-Cys34 of the CHO-derived rhCCL18 resulted in a shift of its activity, reaching the same level as the E. coli-derived rhCCL18. These results demonstrate that the Cys10-Cys34 disulfide bond is involved in the function of CCL18.