Suttichai Krisanaprakornkit and Sakornrat Khongkhunthian
336
apoptosis via a COX-2-dependent mechanism (Chamorro et al, 2009), which is in agreement
with the function of LL-37 in promoting cell proliferation and tissue repair, as indicated
above. Therefore, it is interesting to determine whether LL-37 plays any role in tissue repair
and/or regeneration after periodontal surgery.
Interestingly, exogenously added LL-37 into the wound induces angiogenesis that
corresponds to an
in vitro
study (Koczulla et al, 2003), which demonstrates endothelial cell
proliferation and increased numbers of new blood vessel formation through FPRL1 on
cultured endothelial cell membrane in response to LL-37 treatment. As in keratinocyte
migration, LL-37 also induces migration of human corneal epithelial cells, as well as
expression of IL-1
, IL-6, IL-8, and TNF-
(Huang et al, 2006). Moreover, it has
been shown
that LL-37 can internalize into human lung epithelial cells through endocytosis, and
subsequently accumulates in the perinuclear region (Lau et al, 2005).
There are a number of reports that show other biological effects of neutrophil
-defensins
and human
-defensins on various cell types. For instance,
-defensins enhance mitosis in
some cell types (Murphy et al, 1993), promote tissue repair in airway
epithelial cells via MAP
kinase pathways (Aarbiou et al, 2002), regulate expression for adhesion molecules on
endothelial cells (Chaly et al, 2000), control smooth muscle cell contraction via an
2-
macroglobulin receptor (Nassar et al, 2002), induce proliferation of lung fibroblasts and
collagen synthesis (Han et al, 2009), and induce expression of some mucin genes, i.e.,
MUC5B
and
MUC5AC
(Aarbiou et al, 2004). As with the induction of mucin genes by
neutropil
-defensins, it has lately been demonstrated that LL-37 also up-regulates
MUC2
and
MUC3
expression in intestinal epithelial cell lines (Otte et al, 2009). Furthermore,
-
defensins affect histamine release from mast cell granules through a G-protein coupled
receptor, suggesting their indirect role in vasodilatation (Befus et al, 1999).
Among human
-defensins, hBD-2 activates the differentiation of dental pulp
mesenchymal cells into odontoblast-like cells, confirmed by up-regulation of dentin
sialophosphoprotein (
DSPP
) gene expression (Shiba et al, 2003). In addition, stimulation of
odontoblast-like cells with recombinant hBD-2 leads to increased mRNA expression of
several inflammatory genes, including IL-6, IL-8, and cytosolic phospholipase A
2
(Dommisch
et al, 2007). Consequently, it is probable that hBD-2 plays a role in reparative dentin
formation, as well as immune regulation, in addition to its antimicrobial effect. Furthermore,
like LL-37, hBD-2, hBD-3, and hBD-4 stimulate cell migration and proliferation, and
production of cytokines and chemokines in skin keratinocytes (Niyonsaba et al, 2007).
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