miR-let-7c-5p and miR-149-5p inhibit proinflammatory cytokine production in osteoarthritis and rheumatoid arthritis synovial fibroblasts

Abstract

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common types of arthritis. Both are characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. miRNAs play critical roles in the disease processes of arthritic disorders. However, little is known about the effects of miRNAs on critical inflammatory cytokine production with OA and RA progression. Here, we found higher levels of proinflammatory cytokines including interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in human OA and RA synovial fibroblasts (SFs) compared with normal SFs. Searches of open-source microRNA (miRNA) software determined that miR-let-7c-5p and miR-149-5p interfere with IL-1β, IL-6 and TNF-α transcription; levels of all three proinflammatory cytokines were lower in human OA and RA patients compared with normal controls. Anti-inflammatory agents dexamethasone, celecoxib and indomethacin reduced proinflammatory cytokine production by promoting the expression of miR-let-7c-5p and miR-149-5p. Similarly, ibuprofen and methotrexate also enhanced miR-let-7c-5p and miR-149-5p expression in human SFs. The evidence suggests that increasing miR-let-7c-5p and miR-149-5p expression is a novel strategy for OA and RA.

S1P Increases VEGF Production in Osteoblasts and Facilitates Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-16-5p Expression via the c-Src/FAK Signaling Pathway in Rheumatoid Arthritis

“…In addition, osteoblast-synthesized VEGF enhances EPC angiogenesis during RA progression [7], while we have previously demonstrated that S1P stimulates IL-1β production through the JAK and STAT3 signaling pathways in osteoblasts [20], and the S1P/S1P receptor axis reportedly promotes cyclooxygenase-2 and prostaglandin E2 in RA [21]. Previous research has shown that microRNAs (miRNAs) regulate the progression of RA [22,23], and we have reported miRNA involvement in inflammation and angiogenesis [16,24,25]. Notably, S1P can regulate miRNA expression in human disorders such as cancer and rheumatic disease [26][27][28].…”

A Journey into the Clinical Relevance of Heme Oxygenase 1 for Human Inflammatory Disease and Viral Clearance: Why Does It Matter on the COVID-19 Scene?

“…This effect of HO-1 on HCV replication might be explained partly by the iron dependent inactivation of the HCV RNA polymerase NS5B [ 157 ], and by the BV mediated inhibition of HCV NS3/4A protease and induction of an antiviral response by IFNα2 and IFNα17 [ 153 , 158 ]. Moreover, overexpression of miR-let-7c, which interferes with the production of proinflammatory cytokines in osteoarthritis and rheumatoid arthritis synovial fibroblasts [ 159 ], can reduce HCV replication by targeting HO-1 transcriptional repressor Bach1 [ 160 ].…”

Transcriptome of visceral adipose tissue identifies an inflammation-related ceRNA network that regulates obesity

“…In ammatory factors were increased in patients with obesity [33,34] . Conversely, IL-13 and IL-33, which are anti-in ammatory cytokines, were decreased in obesity [35] . A high-fat diet with IL-33 injection improved insulin sensitivity in an animal study, which indicated that anti-in ammatory treatment could decrease insulin resistance in obesity [35,36] .…”

“…Conversely, IL-13 and IL-33, which are anti-in ammatory cytokines, were decreased in obesity [35] . A high-fat diet with IL-33 injection improved insulin sensitivity in an animal study, which indicated that anti-in ammatory treatment could decrease insulin resistance in obesity [35,36] . In this study, KEGG enrichment showed that pathways including cytokine-cytokine receptor interactions, and TNF and NF-kappa B pathway signaling, regulated obesityrelated in ammation and insulin resistance [37][38][39] .…”