title: Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs.
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.
authors.affiliation: Department of Animal Science, Oklahoma State University, Stillwater, Oklahoma, United States of America ; State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China.
authors.forename: Xiangfang
authors.initials: X
authors.lastname: Zeng
authors.forename: Lakshmi T
authors.initials: LT
authors.lastname: Sunkara
authors.forename: Weiyu
authors.initials: W
authors.lastname: Jiang
authors.forename: Megan
authors.initials: M
authors.lastname: Bible
authors.forename: Scott
authors.initials: S
authors.lastname: Carter
authors.forename: Xi
authors.initials: X
authors.lastname: Ma
authors.forename: Shiyan
authors.initials: S
authors.lastname: Qiao
authors.forename: Guolong
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002087:Butyrates / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D034421:Sus scrofa / Q000235:genetics*; D023083:beta-Defensins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002087:Butyrates; D005232:Fatty Acids, Volatile; D023083:beta-Defensins
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