*7.5.6 Dexamethasone*

It is a synthetic glucocorticoid that is used in the treatment of respiratory, allergic or autoimmune diseases. Its effect is to decrease the expression of proinflammatory cytokine genes through NF-kB. The clinical use of glucocorticoids can increase the susceptibility to infections by decreasing the expression of antimicrobial peptides such as the HBD2. In this study, they investigated the molecular mechanism by which dexamethasone modulated HBD2 expression in response to IL-1b in A549 cells and, the role of MAPKs, MKP-1, AKT, and NF-kB transcription factor. They demonstrated that dexamethasone suppresses the expression of HBD2 for this signaling pathway [83].

### *7.5.7 Isoleucine*

Isoleucine is an essential amino acid that can induce the expression of the HBD2 in the epithelium. Its expression involves the activation of NF-kB/rel family of trans-activating factors. The authors suggest that isoleucine or analogues may have clinical utility as immunostimulants that could bolster the defense of the respiratory epithelium and mucosae [85].

## *7.5.8 Hyaluronic acid*

When the skin epithelium suffers damage, the hyaluronic acid, which is found in the extracellular matrix, is fragmented and activates keratinocytes which in turn stimulate the HBD2 production. The induction is mediated by toll receptors (TLR2 and TLR4) as well as other signaling pathways such as c-Fos and protein kinase C; thus, the epithelium is protected from infections [86].

#### *7.5.9 Sirtuin1 (SIRT1)*

It is a nicotinamide adenine dinucleotide-dependent histone deacetylase, which regulates several processes of the innate and adaptive immune system.

**61**

*Multifunctional Activity of the β-Defensin-2 during Respiratory Infections*

The anti-inflammatory properties of SIRT1 are reportedly known to show [87] that the infection with *S. pneumoniae* in alveolar epithelial cells (A549) induces HBD2 production involving the SIRT1. Furthermore, HBD2 production induced by *S pneumoniae* is mediated by the MAPK activation (p38), and the expression of IL-8

This process has been described in the epithelium of skin and can be achieved by various means, which includes the modulation of cytokines production, cell proliferation and migration and in some cases angiogenesis [88, 89]. It has been demonstrated that HBD2 is expressed in normal skin [90], and its expression increases when the skin is damaged or during the chronic infection [91].

Patients with diabetes mellitus suffer from skin ulcers, and the expression of HBD2 does not increase when compared to normal skin. The scarce expression of HBD2 is seen during the chronic disease. The authors supposed that high glucose

HBD2 is reportedly seen to elicit intracellular Ca+2 mobilization and increased

It is a process by which endothelial cells proliferate and migrate towards the angiogenic stimulus to form new blood vessels. This process is part of the repair of damaged tissues and severe inflammatory processes. The present paper demonstrates that HBD2 stimulates the migration, proliferation and formation of capillary

Peripheral blood mononuclear cells when stimulated by the HBD2 induce a strong cytokine response. The cytokines that were detected in the highest concentration were interleukin 6 (IL-6), interleukin 8 (IL-8) and interleukin 10 (IL10). It was also found that monocyte chemotactic protein 1 (MCP-1) induces a strong response and also induces RANTES, IL-1β, ENA-78 and GRO, so that the induction patterns of cytokines/chemokines can be crucial in the development and amplification of the immune response against pathogenic microorganisms [95].

It has been proven that HBD2 can regulate blood pressure and provide a new

**8. Respiratory diseases associated with the expression of β-defensin-2**

with external medium, and it exposed to a large number of pathogens.

The respiratory epithelium is the largest surface of the human body in contact

mechanism for the treatment of hypertension [96].

keratinocyte migration and proliferation [93]. Besides, this peptide induced phosphorylation of EGFR, signal transducer and activator of transcription STAT1 and STAT3. These are intracellular signaling molecules involved in keratinocyte

levels inhibit the expression of HBD2 in human keratinocytes [92].

*DOI: http://dx.doi.org/10.5772/intechopen.80611*

is regulated by the phosphorylation of ERK.

**7.6 Wound repair**

migration and proliferation.

tubes of endothelial cells [94].

**7.8 Cytokines and chemokines**

**7.7 Angiogenesis**

**7.9 Hypertension**

The anti-inflammatory properties of SIRT1 are reportedly known to show [87] that the infection with *S. pneumoniae* in alveolar epithelial cells (A549) induces HBD2 production involving the SIRT1. Furthermore, HBD2 production induced by *S pneumoniae* is mediated by the MAPK activation (p38), and the expression of IL-8 is regulated by the phosphorylation of ERK.
