| dc.description.abstract | Background. The airway epithelium produces antimicrobial peptides (AMPs) that prevent
colonization of host tissues by a wide range of pathogens. Human β-defensin 2 (hBD-2)
and Cathelicidine are the most well documented AMPs in humans. Several bacterial
products and cholecalciferol have been implicated in the production of these peptides.
Aim of study. To induce the production of hBD-2 and Cahtelicidine after stimulation of
the respiratory epithelia with inactivated bacteria and cholecalciferol.
Methods. First, an in vitro study stimulating A-549 cells with inactivated bacteria and
cholecalciferol was conducted. After that a second in vivo study, where a nasal lavage
(NL) was performed in 12 healthy volunteers in basal conditions, and after a nasal
challenge with separate and subsequent stimuli with either inactivated bacteria (20 million),
cholecalciferol (400 IU), the mixture of inactivated bacteria and cholecalciferol, or shamchallenge
with glycerol plus isotonic saline solution. Finally, immunohistochemistry was
performed in nasal biopsies 48 hours after stimulation with inactivated bacteria to identify
the presence of hBD-2.
Results. We were unable to detect hBD-2 or Cathelicidine by ELISA in the supernatant of
A-549 cell cultures stimulated with inactivated bacteria and/or cholecalficerol. Increased
levels of hBD-2 (4668.99 ± 2829.33 pg/ml) were measured with ELISA in NL fluids
following bacterial challenge. Intriguingly, higher levels of hBD-2 were measured
following the stimulation with the mixture of inactivated bacteria and cholecalciferol, when
a student’s t test for dependent samples was applied (p= 0.013). However, hBD-2
concentrations were below the limit of detection in NL fluids at baseline, and after the
administration of cholecalciferol alone or the sham-challenge. Through
immunohistochemistry, hBD-2 was predominantly localized to the epithelium.
Conclusions. hBD-2 can be induced in the nasal mucosa after administration of inactivated
bacteria. Cholecalciferol could act as a synergistic agent in the production of hBD-2, at
least in the nasal epithelium. Stimulation of the innate immune system to produce hBD-2
could be used to prevent or even treat infections caused by respiratory pathogens.
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Key words: antimicrobial peptides; defensins; host defense; nasal mucosa;
immunostimulants; inactivated bacteria. | |
