Regulation of Human LZIP Expression by NF-κB and Its Involvement in Monocyte Cell Migration Induced by Lkn-1

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 ∼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-κB- and Sp-1-binding sites. Results from an inhibitor assay showed that NF-κB is involved in Lkn-1-induced LZIP expression, but Sp-1 is not. We also demonstrated that NF-κB 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-κB subfamily is specifically involved in Lkn-1-induced chemotaxis. Our findings suggest that transcription factor NF-κB plays an important role in regulation of LZIP expression, and LZIP expression regulates the monocyte cell migration induced by Lkn-1.