title: Regulation of human LZIP expression by NF-kappaB and its involvement in monocyte cell migration induced by Lkn-1.
abstract: Human LZIP is a transcription factor that is involved in leukocyte cell mobility. Expression of LZIP is known to differentially regulate monocyte cell migration induced by CCR1-dependent chemokines. However, its transcriptional regulation has not been characterized. Our results indicate that Lkn-1 induces LZIP expression in a time- and dose-dependent manner, and the induction of LZIP shows an immediate early response to Lkn-1. We identified and cloned approximately 1.4 kb of the LZIP promoter from a human genomic DNA. To identify regulatory elements controlling restricted expression of LZIP, deletion mutants were constructed from the 1469-bp LZIP promoter region (-1219/+251) linked to the luciferase reporter gene. Maximal promoter activity was contained within 613 bp from the tentative transcription initiation site and was sharply reduced in a truncated construct (-338/+251). This promoter sequence contained consensus NF-kappaB- and Sp-1-binding sites. Results from an inhibitor assay showed that NF-kappaB is involved in Lkn-1-induced LZIP expression, but Sp-1 is not. We also demonstrated that NF-kappaB binds to the LZIP promoter and that the binding is specific, as revealed by an electrophoretic mobility shift assay and a mutation analysis. Chemotaxis analysis showed that LZIP expression because of the NF-kappaB subfamily is specifically involved in Lkn-1-induced chemotaxis. Our findings suggest that transcription factor NF-kappaB plays an important role in regulation of LZIP expression, and LZIP expression regulates the monocyte cell migration induced by Lkn-1.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
authors.forename: Sung-Wuk
authors.initials: SW
authors.lastname: Jang
authors.forename: Yoon Suk
authors.initials: YS
authors.lastname: Kim
authors.forename: Yoon Rim
authors.initials: YR
authors.lastname: Kim
authors.forename: Ho Joong
authors.initials: HJ
authors.lastname: Sung
authors.forename: Jesang
authors.initials: J
authors.lastname: Ko
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D019402:Macrophage Inflammatory Proteins; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D015846:Monokines / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000378:metabolism; D013997:Time Factors; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C108814:CCL15 protein, human; C515300:CCR1 protein, human; C107941:CREB3 protein, human; D018925:Chemokines; D019742:Chemokines, CC; D017362:Cyclic AMP Response Element-Binding Protein; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D016328:NF-kappa B; D021122:Protein Subunits; D054389:Receptors, CCR1; D019707:Receptors, Chemokine