# Leucine‐Rich Repeat Containing 15 Promotes the Inflammatory Response in Rheumatoid Arthritis by Regulating NF‐κB Pathway

## TL;DR

This study shows that LRRC15 promotes inflammation in rheumatoid arthritis by activating the NF-κB pathway, and reducing LRRC15 can help reduce joint damage and inflammation.

## Contribution

The study identifies LRRC15 as a novel regulator of the NF-κB pathway in rheumatoid arthritis and demonstrates its role in promoting inflammation.

## Key findings

- LRRC15 is upregulated in CIA rats and IL-1β-treated FLSs, contributing to joint inflammation.
- Silencing LRRC15 reduces joint damage and inflammatory markers like IFN-γ, IL-6, and IL-1β.
- LRRC15 silencing inhibits NF-κB pathway activation by reducing p-p65 and p-IκBα levels.

## Abstract

To explore the influence and molecular mechanism of leucine‐rich repeat containing 15 (LRRC15) in rheumatoid arthritis (RA) model induced by collagen‐induced arthritis (CIA) in rats and interleukin‐1 beta (IL‐1β) treated fibroblast‐like synoviocytes (FLSs).

LRRC15 expression was analyzed using reverse transcription quantitative polymerase chain reaction (RT‐qPCR), western blot analysis, and immunohistochemistry. Hematoxylin‐eosin (H&E) and safranin‐O‐green staining were performed to assess the pathological changes in the joint tissues of rats. The messenger ribonucleic acid (mRNA) and protein expression of interferon gamma (IFN‐γ), interleukin (IL)‐6, IL‐1β, and IL‐10 was detected by RT‐qPCR, enzyme‐linked immunosorbent assay (ELISA), and western blot. Cell proliferation and migration was surveyed using cell counting kit‐8 (CCK‐8), 5‐Ethynyl‐2′‐deoxyuridine (EdU), and Transwell assays. Western blot was applied to detect the protein changes of nuclear factor kappaB (NF‐κB) subunit p65, phosphorylated (p)‐p65, inhibitor of kappa Bα (IκBα), phosphorylated inhibitor kappa Bα (p‐IκBα), and nuclear factor erythroid 2‐related factor 2 (Nrf2).

In CIA rats and IL‐1β‐treated FLSs, LRRC15 expression was upregulated. In vivo, Lrrc15 silencing prevented joint damage, inhibited the expression of IFN‐γ, IL‐6, IL‐1β, and p65, and increased the expression of IL‐10 and IκBα. In vitro, Lrrc15 silencing inhibited the proliferation, migration, and the expression of IFN‐γ, IL‐6, IL‐1β, p‐p65, and p‐IκBα, and increased the expression of IL‐10, IκBα, and Nrf2 in FLSs.

Lrrc15 silencing relieved joint damage and inflammatory response in RA, and this may be associated with the inhibition of the NF‐κB pathway.