β-Defensin 18, a key component of the innate immune system, plays a crucial role in host defense against microbial threats. Functioning as an antimicrobial peptide, it exerts a direct and potent bactericidal effect by disrupting the integrity of microbial membranes. Beyond its immediate antimicrobial function, β-defensin 18 contributes to the modulation of the immune response through intricate interactions with various cellular processes. The activation of β-defensin 18 involves a complex interplay of cellular pathways and biochemical mechanisms. Several chemicals, including epigallocatechin gallate, trichostatin A, quercetin, sulforaphane, curcumin, sodium butyrate, genistein, resveratrol, 5-azacytidine, alpha-lipoic acid, luteolin, and diallyl disulfide, have been identified as activators. These compounds act through diverse pathways, such as NF-κB, histone deacetylation, AP-1, Nrf2/ARE, and DNA methylation, influencing chromatin remodeling, transcription factor activity, and epigenetic modifications. By directly or indirectly affecting these pathways, these chemicals enhance the transcriptional activity of the DEFB18 gene, leading to increased β-defensin 18 expression.
The activation of β-defensin 18 not only reinforces the immediate defense against microbial invaders but also underscores the intricate connections between the innate immune system and various cellular signaling cascades. Understanding the specific pathways involved in β-defensin 18 activation provides insights into potential strategies for enhancing the innate immune response, with implications for host defense and immune modulation.
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