Genomic cloning and promoter analysis of macrophage inflammatory protein (MIP)-2, MIP-1 alpha, and MIP-1 beta, members of the chemokine superfamily of proinflammatory cytokines.

摘要: Macrophage inflammatory protein (MIP)-2, MIP-1 alpha, and beta all belong to the newly recognized "chemokine" superfamily of structurally related, activation-inducible cytokines with growth regulatory activities. We report isolation sequencing genomic clones for murine MIP-2 beta, analyze their sequences in comparison each other several members chemokine family. The (mu)MIP-2 clone displays canonical four exon/three intron structure typical genes alpha subfamily (e.g., IL-8). Potential cis elements proximal promoter region were highly conserved between muMIP-2 its three most closely related human homologs: (hu)GRO-alpha, huGRO-beta, huGRO-gamma. A mouse macrophage cell line, RAW 264.7, was transfected a hormone reporter construct driven by fragment 5' promoter, nested deletion mutant analysis localized LPS responsive element that contains NF kappa B consensus motif lies 51 70 bp from transcription start site. In contrast MIP-2, muMIP-1 exhibited exon/two characteristic family MCP-1). promoters reveals CK-1 element, but transient expression studies 264.7 macrophages fragments either or fused gene link LPS-inducibility both segments near to, not identical with, sequence. Proximal cloned unexpectedly conferred constitutive on macrophage-like cells, initial did this responsiveness known sequence motifs. constitutively active B16 melanoma myelomonocytic line WEHI 3B(A)d-, being times stronger.