RESUMO
Chemokines and chemokine receptors play a role in migration of circulating leukocytes to the region of inflammation. Human LZIP is an uncharacterized transcription factor and is known to participate in leukotactin (Lkn)-1/CCL15-induced cell migration. We investigated the role of human LZIP in expression of CC chemokine receptors (CCRs) and its involvement in monocyte migration. RNase protection analysis showed that LZIP increased mRNA expression of CCR2 and CCR1 in THP-1 cells. Surface expressions of both CCR2 and CCR1 were also increased by LZIP. Results from an electrophoretic mobility shift assay showed that LZIP binds to the C/EBP element in the CCR2 promoter. LZIP also enhanced the chemotactic activities of monocyte chemoattractant protein-1/CCL2 and Lkn-1. These results suggest that LZIP regulates expression of chemokine receptors that are involved in monocyte migration.
Assuntos
Humanos , Aterosclerose/tratamento farmacológico , Proteínas Estimuladoras de Ligação a CCAAT/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Quimiocina CCL2/farmacologia , Quimiocinas CC/farmacologia , Proteínas Inflamatórias de Macrófagos/farmacologia , Monócitos/efeitos dos fármacos , Regiões Promotoras Genéticas , Ligação Proteica , RNA Mensageiro/análise , Receptores CCR1/biossíntese , Receptores CCR2/biossíntese , Ativação Transcricional/efeitos dos fármacos , Transfecção , TransgenesRESUMO
A C6 beta-chemokine, CKbeta8-1, suppressed the colony formation of CD34 + cells of human cord blood (CB). Molecular mechanisms involved in CKbeta8-1-medicated suppression of colony formation of CD34 + cells are not known. To address this issue, the level of various G1/S cell cycle regulating proteins in CKbeta8-1-treated CD34 + cells were compared with those in untreated CD34 + cells. CKbeta8-1 did not significantly alter the expression of the G1/S cycle regulation proteins (cyclin D1, D3, and E), CDK inhibitor (p27and Rb), and other cell proliferation regulation protein (p53) in CB CD34 + cells. Here we describe an in vitro system in which CB CD34 + cells were committed to a multipotent progenitor lineage of colony forming units-granulocyte/macrophage (CFU-GM) by a simple combination of recombinant human (rh) GM-CSF and rhIL-3. In this culture system, we found that cyclin E protein appeared later and disappeared faster in the CKbeta8-1-treated cells than in the control cells during CFU-GM lineage development. These findings suggested that cyclin E may play a role in suppressing the colony formation of CFU-GM by CKbeta8-1.