title: The chemokine-like factor 1 induces asthmatic pathological change by activating nuclear factor-κB signaling pathway.
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 (10μg/ml) added in each well at different times. These results showed that C27 (10μg/ml) time-dependently induced the accumulation of NF-κB in the nucleus of HEK293-CCR4 and A549 cells. In addition, CKLF1 plasmid (100μg) 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.
authors.affiliation: Department of Pharmacology, College of Pharmacy, The Inner Mongolian Medical University, Jinshan Development Zone, Hohhot, Inner Mongolian 010110, China; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, China. Electronic address: cnnmligang@hotmail.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, China.
authors.forename: Guang-yan
authors.initials: GY
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, China.
authors.forename: Zhen-zhen
authors.initials: ZZ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, China.
authors.forename: Hai-jie
authors.initials: HJ
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, China.
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, China.
authors.forename: Jin-feng
authors.initials: JF
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, China.
authors.forename: Yu-he
authors.initials: YH
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, China. Electronic address: chennh@imm.ac.cn.
authors.forename: Nai-hong
authors.initials: NH
authors.lastname: Chen
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D018925:Chemokines / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology; D062792:MARVEL Domain-Containing Proteins / Q000276:immunology*; D008297:Male; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology*; D054398:Receptors, CCR4 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction
chemical_list: C515354:CCR4 protein, human; C000593975:CKLF1 protein, mouse; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins; D016328:NF-kappa B; D054398:Receptors, CCR4
keywords: Asthma; Chemokine-like factor 1; NF-κB