**7.6 Wound repair**

*Immune Response Activation and Immunomodulation*

tions [65].

*7.5.4 Triptolide*

the HBD2 [84].

*7.5.7 Isoleucine*

*7.5.8 Hyaluronic acid*

*7.5.9 Sirtuin1 (SIRT1)*

*7.5.6 Dexamethasone*

for this signaling pathway [83].

respiratory epithelium and mucosae [85].

thus, the epithelium is protected from infections [86].

*7.5.5 Neutrophilic elastase*

gingiva by *P. gingivalis* infection. Further, proteases of the bacteria induced the expression of the defensin through PAR2. The authors suggest that this signaling pathway can lead to the development of preventive therapies in mucosal infec-

This is an immunosuppressive and anti-inflammatory agent that was extracted from an herb of Chinese origin (*Tripterygium wilfordii*). It decreases the expression of the NF-kB and genes related to inflammatory processes. This review chapter shows that this agent suppresses the expression of HBD2 induced by IL-1β in A549

It is a serine protease that is expressed in neutrophils and stored in their granules. It has been reported that neutrophilic elastase in the bronchial epithelium has a direct effect against bacteria; in addition, it can regulate the increased expression of

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

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

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;

It is a nicotinamide adenine dinucleotide-dependent histone deacetylase, which

regulates several processes of the innate and adaptive immune system.

cells and the suppression is associated with the inhibition of NF-kB [83].

**60**

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

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