Induction of human beta-defensin-2 expression in human astrocytes by lipopolysaccharide and cytokines

J Neurochem. 2001 May;77(4):1027-35. doi: 10.1046/j.1471-4159.2001.00305.x.


Defensins are cationic peptides with broad-spectrum antimicrobial activity. They are members of a supergene family consisting of alpha and beta subtypes and each subtype is comprised of a number of different isoforms. For example, human alpha-defensin (HAD) has six isoforms, which are expressed by polymorphonuclear leukocytes and Paneth cells. In contrast, human beta-defensin (HBD) has two isoforms that are expressed by epithelial cells of the skin, gut, respiratory and urogenital tracts. Recently, HBD-1 was detected in human brain biopsy tissue. However, little is known about the expression of HBD-1 or HBD-2 in the CNS and whether neural cells can secrete these peptides. For the present study, human astrocyte, microglial, meningeal fibroblast and neuronal cultures were probed for the expression of HBD-1 and HBD-2 mRNA and protein. Each cell type was either maintained in tissue culture medium alone or in medium containing lipopolysaccharide (LPS) at concentrations ranging from 0.1 to 1 microgram/mL, interleukin-1 beta (IL-1beta) at 1-50 ng/mL, or tumor necrosis factor alpha (TNF-alpha) at the same concentrations. The expression of HBD-1 and HBD-2 mRNAs was monitored by RT-PCR. The cDNA products were sequenced to characterize the gene product. HBD-2 protein was detected by immunoblot, immunoprecipitation and immunocytochemistry. Results of these studies showed that HBD-1 mRNA was detected in all cell cultures except in those enriched for neurons. In contrast, HBD-2 mRNA was detected only in astrocyte cultures that were treated with LPS, IL-1beta or TNF-alpha. The detection of the respective proteins correlated positively with the mRNA results. As such, these data represent the first demonstration of HBD-2 expression by astrocytes and suggest that this peptide may play a role in host defense against bacterial CNS pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Infective Agents
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Cytokines / pharmacology*
  • Female
  • Fetus
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-1 / pharmacology
  • Lipopolysaccharides / pharmacology*
  • Meninges / metabolism
  • Microglia / metabolism
  • Protein Isoforms / genetics
  • RNA, Messenger / genetics
  • Transcription, Genetic / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology
  • beta-Defensins / genetics*


  • Anti-Infective Agents
  • Cytokines
  • DEFB1 protein, human
  • DEFB4A protein, human
  • Interleukin-1
  • Lipopolysaccharides
  • Protein Isoforms
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • beta-Defensins