Anti‑inflammatory role of microRNA‑429 in human gingival epithelial cells‑inhibition of IL‑8 production through direct binding to IKKβ mRNA

Abstract

MicroRNAs (miRNAs), a family of small non-coding RNAs, serve a pivotal role in the regulation of the inflammation by modulating the expression of various genes. However, the molecular mechanism by which miRNAs regulate inflammation-associated molecules in oral epithelial cells remains to be elucidated. The present study examined the biological function of miR-429 by performing the gain-/loss-of-function studies of miR-429 in a gingival squamous cell carcinoma line Ca9-22 cells that either over-or under-expressed miR-429 through transient transfection with miR-429 mimic or miR-429 inhibitor, respectively. The results demonstrated that the over-expression of miR-429 suppressed the mRNA level of several interleukins, including IL-8. In addition, the over-expression of miR-429 reduced IL-8 secretion under the basal and TNF-α stimulated conditions, whereas the secretion of IL-8 was enhanced when miR-429 was under-expressed. The over-expression of miR-429 inhibited the activation of the transcription factor NF-κB. Furthermore, we found that miR-429 suppressed both mRNA and protein levels of IKKβ via its direct binding to the 3'-untranslated region of IKKβ mRNA. In addition, the downregulation of IKKβ by small interfering RNA reduced both NF-kB activity and IL-8 production in Ca9-22 cells. Taken together, the findings revealed the molecular mechanism of miR-429 to regulate the inflammatory mediator in gingival cells and suggested that it could be useful as a therapeutic target of oral inflammatory diseases.

Transcriptomic Characterization of Cow, Donkey and Goat Milk Extracellular Vesicles Reveals Their Anti-Inflammatory and Immunomodulatory Potential

“…Similar effects seem to be addressed to miR-181a with anti-inflammatory effects mediated by the down-regulation of IL-1α [ 90 ] and the inhibition of NF-κB activation [ 91 ]. Furthermore, miR-99a can reduce macrophage M1 phenotype and increase M2 activation by targeting TNFα [ 92 ]; miR-182-5p can modulate the TLR4/NF-κB signaling pathway, inhibiting the inflammatory response induced by LPS treatment [ 93 ], while miR-429 modulates the IL-8 production through the NF-κB inhibition, reducing inflammation in epithelial cells [ 94 ]. Therefore, it was proposed as a candidate for anti-colitis therapy thanks to its capability of modulating mucin secretion in human colorectal cells and mouse colitis tissues [ 95 ].…”

The oral bioaccessibility and gingival cytotoxicity of metal(loid)s in wild vegetables from mining areas: Implication for human oral health

“…Ingesting heavy-metal(loid)-contaminated foods could lead to acute toxicities or chronic accumulations in human tissues and contribute to certain diseases ( 12 ). For instance, periodontitis is a representative inflammatory disease in the gingival tissues ( 13 ). Gingival epithelial cells play important roles in maintaining oral immunologic homeostasis and protecting oral organs from inflammatory damage ( 14 ).…”

Streptococcus gordonii Supragingival Bacterium Oral Infection-Induced Periodontitis and Robust miRNA Expression Kinetics

“…The following supporting information can be downloaded at: . References [ 25 , 50 , 58 , 93 , 99 , 102 , 103 , 108 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 ] are cited in the supplementary file.…”