Cytokines

Recombinant rat CCL17 protein is produced through a robust process. The gene fragment encoding the 24-93 amino acid residues of rat CCL17 is cloned into a vector and inserted into E. coli. This is followed by upstream bioprocessing and downstream purification steps. The final product exhibits a purity exceeding 97% as determined by SDS-PAGE and contains endotoxin levels below 1.0 EU/µg as measured by the LAL method. This recombinant rat CCL17 protein has been validated for its biological activity, demonstrating a concentration-dependent chemotaxis response in human T-lymphocytes within the range of 1.0-10 ng/ml.

Rat CCL17 plays a critical role in the recruitment and activation of Th2 cells, which are key mediators of allergic responses and various inflammatory conditions. This chemokine is constitutively expressed in the thymus and its expression can be induced in various cell types, including peripheral blood mononuclear cells, macrophages, and bronchial epithelial cells [1]. In rat models, CCL17 has been implicated in several pathophysiological conditions, including asthma, pulmonary fibrosis, and responses to environmental pollutants such as cigarette smoke [1][2][3].

The interaction of CCL17 with its receptor, CCR4, is crucial in mediating Th2 cell responses. Studies have shown that CCL17 expression is upregulated in the lungs of rats exposed to various inflammatory stimuli, coinciding with an increase in CCR4-positive lymphocytes, suggesting a role in Th2-dominant immune responses [2][3]. Furthermore, neutralization of CCL17 has been shown to reduce airway hyperresponsiveness in animal models, highlighting its importance in asthma pathogenesis [4][5].

Research has also indicated that CCL17 is involved in the pathophysiology of idiopathic pulmonary fibrosis (IPF). Elevated levels of CCL17 and CCR4 have been observed in models of bleomycin-induced pulmonary fibrosis, emphasizing its role in the recruitment of inflammatory cells to the lung tissue [3].

References:
[1] S. Suzuki, K. Asai, M. Gi, K. Kojima, A. Kakehashi, Y. Oishiet al., Response biomarkers of inhalation exposure to cigarette smoke in the mouse lung, Journal of Toxicologic Pathology, vol. 35, no. 3, p. 247-254, 2022. https://doi.org/10.1293/tox.2021-0077
[2] T. Inoue, S. Fujishima, E. Ikeda, O. Yoshie, N. Tsukamoto, S. Aisoet al., Ccl22 and ccl17 in rat radiation pneumonitis and in human idiopathic pulmonary fibrosis, European Respiratory Journal, vol. 24, no. 1, p. 49-56, 2004. https://doi.org/10.1183/09031936.04.00110203
[3] Y. Yogo, S. Fujishima, T. Inoue, F. Saito, T. Shiomi, K. Yamaguchiet al., Macrophage derived chemokine (ccl22), thymus and activation-regulated chemokine (ccl17), and ccr4 in idiopathic pulmonary fibrosis, Respiratory Research, vol. 10, no. 1, 2009. https://doi.org/10.1186/1465-9921-10-80
[4] S. Santulli-Marotto, K. Boakye, E. Lacy, S. Wu, J. Luongo, K. Kavalkovichet al., Engagement of two distinct binding domains on ccl17 is required for signaling through ccr4 and establishment of localized inflammatory conditions in the lung, Plos One, vol. 8, no. 12, p. e81465, 2013. https://doi.org/10.1371/journal.pone.0081465
[5] S. Santulli-Marotto, J. Fisher, T. Petley, K. Boakye, T. Panavas, J. Luongoet al., Surrogate antibodies that specifically bind and neutralize ccl17 but not ccl22, Monoclonal Antibodies in Immunodiagnosis and Immunotherapy, vol. 32, no. 3, p. 162-171, 2013. https://doi.org/10.1089/mab.2012.0112