| Scope and Method of Study: The focus of this study is to evaluate a broad range of free fatty acids and their derivatives for the efficacy in the specific regulation of LL-37, whose synthesis has the potential for disease control and prevention without using conventional antibiotics. A human colon adenocarcinoma cell line, HT-29, and a human leukemic monocytic cell line, U-937, were used in the study. They were seeded at a density of 1x 106 cells/well and treated with either solvents or different concentration of individual agents for 24-h prior to cell harvesting. All chemicals were tested for their cytotoxicity and only the subtoxic concentrations of the chemicals were used to determine their effect on LL-37 gene expression. Total RNA was isolated to synthesize the first-strand of cDNA. Real time RT-PCR was conducted subsequently to quantitatively analyze LL-37 expression level changes in each sample using comparative DeltaDeltaCt method.;Findings and Conclusions: It was revealed by our study that hexanoate and heptanoate with 6 and 7 carbons in the aliphatic chain were more potent that 4-carbon butyrate in promoting LL-37 gene expression in both cell types. 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 with favorable smells such as benzyl butyrate, trans -cinnamyl butyrate, 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. Discovery of many fatty acids and their analogs with a strong capacity to augment LL-37 synthesis may have potential for further development as immune boosting dietary supplements for antimicrobial therapy. |
