Abstract
Dietary modulation of the synthesis of endogenous host defense peptides (HDPs) represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2), pBD3, epididymis protein 2 splicing variant C (pEP2C), and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3–8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.
Highlights
Infectious diseases continue to pose significant economic losses to the animal industry
It is known that LL-37 mRNA and protein expressions are concurrently augmented in humans and rabbits following butyrate administration [25,38], and that butyrateinduced host defense peptides (HDPs) mRNA expression is associated with an enhanced antibacterial activity of monocytes and bacterial clearance in chickens [26]
It is still important to confirm the up-regulation of porcine HDPs at the protein levels, in vivo, and the subsequent effect on disease resistance and pathogen reduction in pigs in the future
Summary
Infectious diseases continue to pose significant economic losses to the animal industry. Dietary compounds with the capacity to augment HDP synthesis and host immunity are attractive candidates as alternatives to antibiotics for disease control and prevention [3]. As a critically important first line of defense, HDPs are produced mainly by both mucosal epithelial cells and phagocytes in vertebrate animals [4,5]. These peptides are broadly active against a range of pathogens including antibiotic-resistant strains. Unlike conventional antibiotics with no immune regulatory functions, HDPs are capable of modulating the host immune system by recruiting and activating different types of immune cells [6]. Most HDPs have the capacity to dampen the bacterial infection-induced inflammatory response, because of their strong affinity for bacterial membrane components such as lipopolysaccharides [7]
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