Discovery of new human β-defensins using a genomics-based approach

Hong Peng Jia, Brian C. Schutte, Andreas Schudy, Rose Linzmeier, Janet M. Guthmiller, Georgia K. Johnson, Brian F. Tack, Joseph P. Mitros, Andre Rosenthal, Tomas Ganz, Paul B. McCray

Research output: Contribution to journalArticle

229 Scopus citations

Abstract

Epithelial β-defensins are broad-spectrum cationic antimicrobial peptides that also act as chemokines for adaptive immune cells. In the human genome, all known defensin genes cluster to a <1 Mb region of chromosome 8p22-p23. To identify new defensin genes, the DNA sequence from a contig of large-insert genomic clones from the region containing human β-defensin-2 (HBD-2) was analyzed for the presence of defensin genes. This sequence survey identified a novel β-defensin, termed HBD-3. The HBD-3 gene contains two exons, is located 13 kb upstream from the HBD-2 gene, and it is transcribed in the same direction. A partial HBD-3 cDNA clone was amplified from cDNA derived from IL-1β induced fetal lung tissue. The cDNA sequence encodes for a 67 amino acid peptide that is ∼43% identical to HBD-2 and shares the β-defensin six cysteine motif. By PCR analysis of two commercial cDNA panels, HBD-3 expression was detected in adult heart, skeletal muscle, placenta and in fetal thymus. From RT-PCR experiments, HBD-3 expression was observed in skin, esophagus, gingival keratinocytes, placenta and trachea. Furthermore, in fetal lung explants and gingival keratinocytes, HBD-3 mRNA expression was induced by IL-1β. Additional sequence analysis identified the HE2 (human epididymis secretory protein) gene 17 kb upstream from the HBD-3 gene. One splice variant of this gene (HE2β1) encodes a β-defensin consensus cysteine motif, suggesting it represents a defensin gene product. HE2β1 mRNA expression was detected in gingival keratinocytes and bronchial epithelia using RT-PCR analysis. The discovery of these novel β-defensin genes may allow further understanding of the role of defensins in host immunity at mucosal surfaces.

Original languageEnglish (US)
Pages (from-to)211-218
Number of pages8
JournalGene
Volume263
Issue number1-2
DOIs
StatePublished - Jan 24 2001

Keywords

  • Bacterial artificial chromosome
  • Chromosome 8
  • Contiguous sequence
  • Interleukin-1β
  • NFκB

ASJC Scopus subject areas

  • Genetics

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  • Cite this

    Peng Jia, H., Schutte, B. C., Schudy, A., Linzmeier, R., Guthmiller, J. M., Johnson, G. K., Tack, B. F., Mitros, J. P., Rosenthal, A., Ganz, T., & McCray, P. B. (2001). Discovery of new human β-defensins using a genomics-based approach. Gene, 263(1-2), 211-218. https://doi.org/10.1016/S0378-1119(00)00569-2