Abstract
Enhancing the synthesis of microbicidal and immunomodulatory host defense peptides (HDP) is a promising host-directed antimicrobial strategy to combat a growing threat of antimicrobial resistance. Here we investigated the effect of several natural cyclooxygenase-2 (COX-2) inhibitors on chicken HDP gene regulation. Our results indicated that phenolic COX-2 inhibitors such as quercetin, resveratrol, epigallocatechin gallate, anacardic acid, and garcinol enhanced HDP gene expression in chicken HTC macrophage cell line and peripheral blood mononuclear cells (PBMCs). Moreover, these natural COX-2 inhibitors showed a strong synergy with butyrate in augmenting the expressions of multiple HDP genes in HTC cells and PBMCs. Additionally, quercetin and butyrate synergistically promoted the expressions of mucin-2 and claudin-1, two major genes involved in barrier function, while suppressing lipopolysaccharide-triggered interleukin-1β expression in HTC macrophages. Mechanistically, we revealed that NF-κB, p38 mitogen-activated protein kinase, and cyclic adenosine monophosphate signaling pathways were all involved in the avian β-defensin 9 gene induction, but histone H4 was not hyperacetylated in response to a combination of butyrate and quercetin. Because of their HDP-inducing, barrier-protective, and antiinflammatory activities, these natural COX-2 inhibitors, when combined with butyrate, may be developed as novel host-directed antimicrobial therapeutics.
Highlights
The rapid emergence of antibiotic-resistant bacteria has become a major public health concern [1], creating an urgent need for the development of novel antimicrobial therapeutic strategies with a minimum risk to trigger resistance [2]
A range of small-molecule compounds such as short-chain fatty acids, vitamin D3, and histone deacetylase (HDAC) inhibitors have been found to be capable of inducing host defense peptides (HDPs) synthesis and some have been explored for disease control and prevention [3,4,5, 10, 11]
To study whether chicken HDP genes are regulated by quercetin, both dose-response and time-course experiments were conducted with quercetin in chicken HTC macrophage cells
Summary
The rapid emergence of antibiotic-resistant bacteria has become a major public health concern [1], creating an urgent need for the development of novel antimicrobial therapeutic strategies with a minimum risk to trigger resistance [2]. Boosting host innate immunity through induction of endogenous host defense peptide (HDP) synthesis has attracted an increasing attention as a hostdirected antiinfective approach [3,4,5]. HDPs, known as antimicrobial peptides, are a group of small cationic and amphipathic peptides with preferential expression in phagocytes and epithelial cells of the host [6]. HDPs consist mainly of the defensin or cathelicidin families in vertebrates. Chicken HDPs are widely expressed in the respiratory, gastrointestinal, and urogenital tracts as well as in multiple lymphoid cells, and regulated differentially in response to infection and inflammation [7, 8]. Immunomodulatory, and barrier protective activities, HDPs constitute a critically important component of the innate immunity system [6, 9]. A range of small-molecule compounds such as short-chain fatty acids, vitamin D3, and histone deacetylase (HDAC) inhibitors have been found to be capable of inducing HDP synthesis and some have been explored for disease control and prevention [3,4,5, 10, 11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
