Human beta defensin 2 promotes intestinal wound healing in vitro

Abstract

Limiting microbial threats, maintenance and re-establishment of the mucosal barrier are vital for intestinal homeostasis. Antimicrobial peptides have been recognized as essential defence molecules and decreased expression of these peptides has been attributed to chronic inflammation of the human intestinal mucosa. Recently, pluripotent properties, including stimulation of proliferation and migration have been suggested for a number of antimicrobial peptides. However, it is currently unknown, whether the human beta-defensin 2 (hBD-2) in addition to its known antimicrobial properties has further effects on healing and protection of the intestinal epithelial barrier. Caco-2 and HT-29 cells were stimulated with 0.1-10 microg/ml hBD-2 for 6-72 h. Effects on cell viability and apoptosis were monitored and proliferation was quantified by bromo-deoxyuridine incorporation. Migration was quantified in wounding assays and characterized by immunohistochemistry. Expression of mucins was determined by quantitative PCR and slot-blot analysis. Furthermore, anti-apoptotic capacities of hBD-2 were studied. Over a broad range of concentrations and stimulation periods, hBD-2 was well tolerated by IECs and did not induce apoptosis. hBD-2 significantly increased migration but not proliferation of intestinal epithelial cells. Furthermore, hBD-2 induced cell line specific the expression of mucins 2 and 3 and ameliorated TNF-related apoptosis-inducing ligand (TRAIL) induced apoptosis. In addition to its known antimicrobial properties, hBD-2 might have further protective effects on the intestinal epithelium. Results of this in vitro study suggest, that hBD-2 expression may play a dual role in vivo, i.e. in impaired intestinal barrier function observed in patients with inflammatory bowel disease.

Streptococcus pneumoniaeinduces human β-defensin-2 and -3 in human lung epithelium

“…However, the measured hBD-2 and hBD-3 concentrations from the above-mentioned studies and in our data were low. This prompted us to the assumption that these defensins might preferentially modulate the host immune response by providing an interface between innate and adaptive immune response and promote repair mechanisms in the course of pneumococci pneumonia [9,13,14]. Nevertheless, hBD-2 and hBD-3 might accumulate onto the pulmonary mucosa and display alone or synergistically with other antimicrobial proteins (AMPs) their antimicrobial function in pneumonia.…”

“…They modulate cytokine response and selectively chemoattract immune effector cells to the site of inflammation [9]. hBD-2 and hBD-3 promote wound healing by inducing increased cell proliferation [13,14]. Both defensins are expressed in the cells of various mucosal epithelia, including those of the airway [11,12,[15][16][17][18][19].…”

CCR6 Regulation of the Actin Cytoskeleton Orchestrates Human Beta Defensin-2- and CCL20-mediated Restitution of Colonic Epithelial Cells

“…Other investigators have recently shown that HBD2 induces epithelial migration at 1000 ng/ml in the transformed HT29 intestinal cell line (54). In marked contrast, we chose to focus our studies using 20 ng/ml of HBD2, because that concentration is within bactericidal range of the molecule (55) and approximates the concentration of HBD2 observed in human gastric juices and human bronchoalveolar lavage (56).…”

Tiger shrimp (Penaeus monodon) penaeidin possesses cytokine features to promote integrin-mediated granulocyte and semi-granulocyte adhesion

“…In humans, the mammalian AMPs HBD and LL-37 chemoattract white blood cells and promote epithelial cell migration in wound healing [9,41,43,44]. Hemocytes play critical roles in invertebrate immune and wound-repair systems [45].…”