Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5832811 | International Immunopharmacology | 2014 | 8 Pages |
Abstract
CKLF1, which exhibits chemotactic activities on a wide spectrum of leukocytes, is up-regulated during the progress of asthma. It plays a vital role in the pathogenesis of pulmonary disease. Here, we report that CKLF1 has the capability to activate the NF-κB signaling pathway leading to the pathological change in the lung. The HEK293-CCR4 cell line, which expressed CCR4 stably, was established and screened. Western blot analysis was performed to determine the expression of NF-κB in HEK293-CCR4 and A549 cells following the C27 (10 μg/ml) added in each well at different times. These results showed that C27 (10 μg/ml) time-dependently induced the accumulation of NF-κB in the nucleus of HEK293-CCR4 and A549 cells. In addition, CKLF1 plasmid (100 μg) injection and electroporation led to the asthmatic change in the lung in mice as shown by HE and PAS staining. Furthermore, it was confirmed that CKLF1 significantly up-regulated the p-IκB expression, decreased the IκB expression, and suppressed the NF-κB expression in the cytoplasm of pulmonary tissue in vivo study. Intriguingly, an enhanced nuclear accumulation of NF-κB was observed in the lung of pCDI-CKLF1 electroporated mice, compared to that in the sham group. Therefore, the NF-κB signaling pathway was involved in the asthmatic change induced by CKLF1, among which CCR4 might play a crucial role.
Keywords
CCR4MDC/CCL22CC chemokine receptor 4TARC/CCL17C19T helper type 2RPMI-1640Roswell Park Memorial Institute 1640A549IL-13IL-5CKLF1CXCR4PBMCsMDCHEK293FBSNF-κBFITCIL-4DEXWBCSDF-1PBSAsthmainterleukin 13Interleukin 4Interleukin 5thymus and activation-regulated chemokinetumor necrosis factor-alphaDexamethasoneSARSTARCfetal bovine serumTH2 cellshuman embryonic kidney 293 cellsperipheral blood mononuclear cellssevere acute respiratory syndromestromal cell-derived factor-1Chemokine-like factor 1TNF-αnuclear factor kappa Bphosphate buffer salinefluorescein isothiocyanateBronchoalveolar lavage fluidMacrophage-derived chemokinewhite blood cellCXC chemokine receptor 4
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Authors
Gang Li, Guang-yan Li, Zhen-zhen Wang, Hai-jie Ji, Dong-mei Wang, Jin-feng Hu, Yu-he Yuan, Gang Liu, Nai-hong Chen,