microRNA-210 and microRNA-3570 Negatively Regulate NF-κB-Mediated Inflammatory Responses by Targeting RIPK2 in Teleost Fish

Abstract

Pathogen infection can cause the production of inflammatory cytokines, which are key mediators that cause the host’s innate immune response. Therefore, proper regulation of immune genes associated with inflammation is essential for immune response. Among them, microRNAs (miRNAs) as gene regulator have been widely reported to be involved in the innate immune response of mammals. However, the regulatory network in which miRNAs are involved in the development of inflammation is largely unknown in lower vertebrates. Here, we identified two miRNAs from miiuy croaker (Miichthys miiuy), miR-210 and miR-3570, which play a negative regulatory role in host antibacterial immunity. We found that the expressions of miR-210 and miR-3570 were significantly upregulated under the stimulation of Gram-negative bacterium vibrio harveyi and LPS (lipopolysaccharide). Induced miR-210 and miR-3570 inhibit inflammatory cytokine production by targeting RIPK2, thereby avoiding excessive inflammation. In particular, we found that miR-210 and miR-3570 negatively regulate antimicrobial immunity by regulating the RIPK2-mediated NF-κB signaling pathway. The collective results indicated that both miRNAs are used as negative feedback regulators to regulate RIPK2-mediated NF-κB signaling pathway and thus play a regulatory role in bacteria-induced inflammatory response.

Long Noncoding RNA MIR122HG Inhibits MAVS-Mediated Antiviral Immune Response by Deriving miR-122 in Miiuy Croaker (Miichthys miiuy)

“…EPC cells were cultured, briefly, in medium 199 (Hyclone), containing 10% fetal bovine serum (FBS, Gibco), 100 mg/mL streptomycin, and 100 U/mL penicillin under 5% CO 2 at 28 °C, as described previously [ 38 ]. HEK293 cells were cultured in DMEM high-glucose medium (HyClone) containing 10% FBS, 100 mg/mL streptomycin and 100 U/mL penicillin 5% CO 2 at 37°C [ 39 ].…”

Non-coding RNAs targeting NF-κB pathways in aquatic animals: A review

“…Key members of the NLR pathways include the NLR family members nucleotide oligomerization domain 1 and 2 (NOD1 and NOD2), receptor interacting serine/threonine kinase 2 (RIPK2), NEMO, IKKs (IKKα and IKKβ), and p50/p65. In aquatic animals, several members of the NLR pathway have been identified, including NOD1 ( 48 , 100 ) and RIPK2 ( 101 ).…”

“…miR-210 and miR-3570 are two known miRNAs having regulatory relationships with RIPK2 homologs ( 101 ). miR-210 and miR-3570 are both 22 nt in length, with seed regions “-CCACUG-” (miR-210) and “-CUGUU-” (miR-3570), respectively.…”

Identification and expression profiling of receptor‐interacting serine/threonine‐protein kinase 2 in Siberian sturgeon (Acipenser baerii)

“…In lower vertebrates, RIPK2 has been reported in zebrafish ( Danio rerio ) (Chang et al ., 2010), catla ( Catla catla ) (Swain, Maiti, & Samanta, 2013), rohu ( Labeo rohita ) (Swain et al ., 2012), orange‐spotted grouper ( Epinephelus coioides ) (Hou et al ., 2012), goldfish ( Carassius auratus L.) (Xie & Belosevic, 2015), mrigal ( Cirrhinus mrigala ) (Swain, Basu, & Samanta, 2013), Japanese flounder ( Paralichthys olivaceus ) (Liu et al ., 2018), miiuy croaker ( Miichthys miiuy ) (Su et al ., 2021) and rainbow trout ( Oncorhynchus mykiss ) (Jang et al ., 2016). The expression of lipopolysaccharide (LPS)‐induced inflammatory cytokines was inhibited after siRNA interfered with RIPK2 in miiuy croaker (Su et al ., 2021). Overexpression of the RIPK2 can activate the NF‐κB signalling pathway in goldfish and miiuy croaker (Bi et al ., 2018; Xie & Belosevic, 2015).…”