1. β-defensin 2 ameliorates lung injury caused by Pseudomonas infection and regulates proinflammatory and anti-inflammatory cytokines in rat
Zhenwei Shen, Lu Fang, Liming Zhao, Han Lei Int J Mol Sci. 2014 Jul 30;15(8):13372-87. doi: 10.3390/ijms150813372.
An important member of the defensin family, β-defensin 2, is believed to play an important role in defense against foreign pathogens. In the present study, we constructed lentiviral vectors to express and knockdown β-defensin 2 in rat lungs. The results showed that the infection of β-defensin 2 overexpression lentivirus and β-defensin 2 shRNA effectively increased and suppressed the expression of β-defensin 2 in rat lung, respectively. The overexpression of β-defensin 2 mediated by the lentiviral vector protected lung from infection of Pseudomonas aeruginosa, but shRNA targeting β-defensin 2 aggregated the damage of lung. In addition, we also found that β-defensin 2 overexpression increased basal expression of anti-inflammatory cytokine such as IL-4, IL-10 and IL-13 and decreased levels of proinflammatory cytokines which include IL-1α, IL-1β, IL-5, IL-6, IL-8, IL-18, and TNF-α. Moreover, in the process of cytokine regulation, NF-κB pathway may be involved. Taken together, these data suggest that β-defensin 2 has protective effects against infection of Pseudomonas aeruginosa in rat and plays a role in inflammatory regulation by adjusting cytokine levels.
2. Effects of Apigenin on RBL-2H3, RAW264.7, and HaCaT Cells: Anti-Allergic, Anti-Inflammatory, and Skin-Protective Activities
Che-Hwon Park, Seon-Young Min, Hye-Won Yu, Kyungmin Kim, Suyeong Kim, Hye-Ja Lee, Ji-Hye Kim, Young-Jin Park Int J Mol Sci. 2020 Jun 29;21(13):4620. doi: 10.3390/ijms21134620.
Apigenin (4',5,7-trihydroxyflavone, flavonoid) is a phenolic compound that is known to reduce the risk of chronic disease owing to its low toxicity. The first study on apigenin analyzed its effect on histamine release in the 1950s. Since then, anti-mutation and antitumor properties of apigenin have been widely reported. In the present study, we evaluated the apigenin-mediated amelioration of skin disease and investigated its applicability as a functional ingredient, especially in cosmetics. The effect of apigenin on RAW264.7 (murine macrophage), RBL-2H3 (rat basophilic leukemia), and HaCaT (human immortalized keratinocyte) cells were analyzed. Apigenin (100 μM) significantly inhibited nitric oxide (NO) production, cytokine expression (interleukin (IL)-1β, IL6, cyclooxygenase (COX)-2, and inducible nitric oxide synthase [iNOS]), and phosphorylation of mitogen-activated protein kinase (MAPK) signal molecules, including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) in RAW264.7 cells. Apigenin (30 M) also inhibited the phosphorylation of signaling molecules (Lyn, Syk, phospholipase Cγ1, ERK, and JNK) and the expression of high-affinity IgE receptor FcεRIα and cytokines (tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-6, IL-13, and COX-2) that are known to induce inflammation and allergic responses in RBL-2H3 cells. Further, apigenin (20 μM) significantly induced the expression of filaggrin, loricrin, aquaporin-3, hyaluronic acid, hyaluronic acid synthase (HAS)-1, HAS-2, and HAS-3 in HaCaT cells that are the main components of the physical barrier of the skin. Moreover, it promoted the expression of human β-defensin (HBD)-1, HBD-2, HBD-3, and cathelicidin (LL-37) in HaCaT cells. These antimicrobial peptides are known to play an important role in the skin as chemical barriers. Apigenin significantly suppressed the inflammatory and allergic responses of RAW264.7 and RBL cells, respectively, and would, therefore, serve as a potential prophylactic and therapeutic agent for immune-related diseases. Apigenin could also be used to improve the functions of the physical and chemical skin barriers and to alleviate psoriasis, acne, and atopic dermatitis.
3. Human β-defensin 3 gene modification promotes the osteogenic differentiation of human periodontal ligament cells and bone repair in periodontitis
Lingjun Li, Han Jiang, Rixin Chen, Jing Zhou, Yin Xiao, Yangheng Zhang, Fuhua Yan Int J Oral Sci. 2020 Apr 29;12(1):13. doi: 10.1038/s41368-020-0078-6.
Efforts to control inflammation and achieve better tissue repair in the treatment of periodontitis have been ongoing for years. Human β-defensin 3, a broad-spectrum antimicrobial peptide has been proven to have a variety of biological functions in periodontitis; however, relatively few reports have addressed the effects of human periodontal ligament cells (hPDLCs) on osteogenic differentiation. In this study, we evaluated the osteogenic effects of hPDLCs with an adenoviral vector encoding human β-defensin 3 in an inflammatory microenvironment. Then human β-defensin 3 gene-modified rat periodontal ligament cells were transplanted into rats with experimental periodontitis to observe their effects on periodontal bone repair. We found that the human β-defensin 3 gene-modified hPDLCs presented with high levels of osteogenesis-related gene expression and calcium deposition. Furthermore, the p38 MAPK pathway was activated in this process. In vivo, human β-defensin 3 gene-transfected rat PDLCs promoted bone repair in SD rats with periodontitis, and the p38 mitogen-activated protein kinase (MAPK) pathway might also have been involved. These findings demonstrate that human β-defensin 3 accelerates osteogenesis and that human β-defensin 3 gene modification may offer a potential approach to promote bone repair in patients with periodontitis.
