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Mammalian innate and acquired immune responses involve a coordinated, sequential, and self limiting sequence of events controlled by positive and negative regulatory mechanism. MicroRNAs have been implicated as a negative regulator for diverse biological events including immune responses. However, the involvement of miRNAs in regulating the immune responses is just beginning to be explored. Here, we characterized the expression profiling of 375 microRNAs in porcine monocytes induced by lipopolysaccharide (LPS), and result shows that several of them are endotoxin-responsive genes. Through promoter analysis, the miR-628 was found to be a NF-κB dependent gene. Importantly, miR-628 was predicted to base-pair with sequences in the 3'-UTR of the myeloid differentiation protein 88 (MyD88) gene. And we found that the UTR inhibit expression of a linked reporter gene coding a key adapter molecule downstream of Toll-like receptors (TLRs), resulting in suppressing of the TLR signaling. Therefore, we not only propose a role of miR-628 in control of the TLR signaling through a negative feedback regulation loop involving down-regulation of MyD88 protein levels, but results may also contribute to rational target selection orchestrating the inflammatory responses.