Mouse CCL6 ELISA Kit

To elucidate genes important in development or repair of asbestos-induced lung diseases, gene expression was examined in mice after inhalation of chrysotile asbestos for 3, 9, and 40 days. We identified changes in the expression of genes linked to proliferation (cyclin B2, CDC20, and CDC28 protein kinase regulatory subunit 2), inflammation (CCL9, CCL6, complement component 1, chitinase3-like 3, TNF superfamily member 10, and IL-1B), and matrix remodeling (MMP12, MMP3, integrin alpha X, and cathepsins K, Z, B, and S). The most highly induced gene at all time points was mclca3 (gob5), a putative calcium-activated chloride channel involved in the regulation of mucus production and/or secretion. Using histochemistry, we demonstrated accumulation of mucus and increased mClca3 protein in the bronchiolar epithelium of asbestos-exposed mice at all time points but peaking at 9 days. Cytokine levels (interleukin-1 beta, interleukin-4, interleukin-6) in bronchoalveolar lavage fluid also increased at 9 days, suggesting Th2-mediated immunity may play a role in asbestos-induced mucus production. In contrast, levels of cathepsin K, a potent elastase, increased between 3 and 40 days at both the mRNA and protein levels, localizing primarily in CD45-positive leukocytes and interstitial cells. Identification of genes involved in lung injury and remodeling after asbestos exposure could aid in defining mechanisms of airborne particulate-induced disease and in developing therapeutic strategies.

The CCL6 chemokine gene was identified as a direct positive target of the L-Myc oncoprotein in interleukin 3-dependent 32D myeloid cells. A mutant form of c-Myc, lacking a region of the NH2-terminal domain necessary for transcriptional repression (c-MycDeltaMBII), also up-regulated CCL6. Chromatin immunoprecipitation showed that L-Myc, c-MycDeltaMBII, and full-length c-Myc all bound the CCL6 promoter, although the latter was inactive in transcriptional up-regulation. Exogenously added CCL6 induced marked apoptosis in some cell types. However, in 32D cells, the coexpression of c-Myc and CCL6 abrogated interleukin 3 dependence and produced a highly leukemogenic phenotype. In two solid tumor models, CCL6 overexpression also accelerated tumor growth, and/or enhanced local and metastatic spread in association with marked apoptosis of the tumor capsule and adjacent normal tissues. Our results show that CCL6 can be either a positive or negative target for Myc oncoproteins. The chemokine may alter tumor behavior by relieving its growth factor dependency and by promoting invasiveness as a result of local tissue apoptosis.