Innate immune peptide LL-37 displays distinct expression pattern from beta-defensins in inflamed gingival tissue

Abstract

SummaryAnti-microbial peptides produced from mucosal epithelium appear to play pivotal roles in the host innate immune defence system in the oral cavity. In particular, human beta-defensins (hBDs) and the cathelicidin-type antimicrobial peptide, LL-37, were reported to kill periodontal disease-associated bacteria. In contrast to well-studied hBDs, little is known about the expression profiles of LL-37 in gingival tissue. In this study, the anti-microbial peptides expressed in gingival tissue were analysed using immunohistochemistry and enxyme-linked immunosorbent assay (ELISA). Immunohistochemistry revealed that neutrophils expressed only LL-37, but not hBD-2 or hBD-3, and that such expression was prominent in the inflammatory lesions when compared to healthy gingivae which showed very few or no LL-37 expressing neutrophils. Gingival epithelial cells (GEC), however, expressed all three examined anti-microbial peptides, irrespective of the presence or absence of inflammation. Moreover, as determined by ELISA, the concentration of LL-37 in the gingival tissue homogenates determined was correlated positively with the depth of the gingival crevice. Stimulation with periodontal bacteria in vitro induced both hBD-2 and LL-37 expressions by GEC, whereas peripheral blood neutrophils produced only LL-37 production, but not hBD-2, in response to the bacterial stimulation. These findings suggest that LL-37 displays distinct expression patterns from those of hBDs in gingival tissue.

Periodontal Disease and Gingival Innate Immunity – Who Has the Upper Hand?

“…In addition, compared to the samples from healthy subjects, the level of beta-defensin mRNA expression was lower and less frequently found in samples from periodontitis patients (Dunsche, Acil et al 2002;Bissell, Joly et al 2004). Similar results have also been reported testing mRNA level by in situ hybridization and protein level using immunohistochemistry (Lu, Jin et al 2004;Lu, Samaranayake et al 2005;Hosokawa, Hosokawa et al 2006). These studies suggest a decrease in the expression of hBD-2 and hBD-3 in both patient groups of gingivitis and periodontitis.…”

“…The levels of AMPs in GCF are thought to be associated with periodontal disease, as demonstrated by Puklo et al that the GCF HNP1-3 levels were higher in patients with aggressive or chronic periodontitis when compared to healthy controls (Puklo, Guentsch et al 2008). Gingival tissue samples from chronic periodontitis patients showed elevated mRNA expression and higher immunostaining of LL-37 on neutrophils, while the LL-37 levels were also elevated in the GCF of periodontitis patients (Hosokawa, Hosokawa et al 2006;Turkoglu, Emingil et al 2009;Turkoglu, Kandiloglu et al 2011). In addition, patients with morbus Kostmann syndrome, an inherited disorder that causes lower than normal levels of neutrophils, have been found to be more susceptible to periodontal disease, while those with a bone marrow transplant are not (Putsep, Carlsson et al 2002).…”

Intracellular Receptor for Human Host Defense Peptide LL-37 in Monocytes

“…All immunoblots resulted in the detection of a product at 37 kDa that contained 5 The online version of this article contains supplemental material.…”

Expression and Possible Immune-regulatory Function of Ghrelin in Oral Epithelium

“…Immortalized human oral epithelial cell lines RT7 and OBA9 were cultured in Keratinocytes-SFM (Invitrogen, Carlsbad, CA, USA), as described previously (Hosokawa et al, 2006;Ohta et al, 2008). Immortalized human oral epithelial cell line OKF6/ TERT-2 cells were kindly provided by James G. Rheinwald (Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, MA, USA) (Dickson et al, 2000).…”