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Differential regulation of human cathelicidin LL-37 by free fatty acids and their analogs

Author:
Jiang, Weiyu, Sunkara, Lakshmi T., Zeng, Xiangfang, Deng, Zhuo, Myers, Sarah M., Zhang, Guolong
Source:
Peptides 2013 v.50 pp. 129-138
ISSN:
0196-9781
Subject:
butyrates, cathelicidins, dietary supplements, disease control, drug therapy, epithelial cells, free fatty acids, gene expression, humans, immunomodulation, inflammation, medium chain fatty acids, reverse transcriptase polymerase chain reaction, short chain fatty acids, sodium
Abstract:
LL-37 is the single cathelicidin host defense peptide in humans with direct antimicrobial and immunomodulatory activities. Specific regulation of LL-37 synthesis has emerged as a novel non-antibiotic approach to disease control and prevention. Short-chain fatty acids, and butyrate in particular, were found recently to be strong inducers of LL-37 gene expression without causing inflammation. Here, we further evaluated the LL-37-inducing efficiency of a broad range of saturated free fatty acids and their derivatives in human HT-29 colonic epithelial cells and U-937 monocytic cells by real-time RT-PCR. Surprisingly, we revealed that valerate, hexanoate, and heptanoate with 5–7 carbons are more potent than 4-carbon butyrate in promoting LL-37 gene expression in both cell types. Free fatty acids with longer than 7 or shorter than 4 carbons showed only a marginal effect on LL-37 expression. Studies with a series of fatty acid derivatives with modifications in the aliphatic chain or carboxylic acid group yielded several analogs such as benzyl butyrate, trans-cinnamyl butyrate, glyceryl tributyrate, and phenethyl butyrate with a comparable LL-37-inducing activity to sodium butyrate. On the other hand, although reactive, the anhydride derivatives of short- and medium-chain fatty acids are as potent as their corresponding free acid forms in LL-37 induction. Thus, these newly identified free fatty acids and their analogs with a strong capacity to augment LL-37 synthesis may hold promise as immune boosting dietary supplements for antimicrobial therapy.
Agid:
1054889